Favipiravir
Originally developed to treat flu and marketed in Japan as Avigan, promising Covid-19 trial results have seen countries stockpiling this medication by the millions
BY BEN VALSLER 31 JULY 2020 CHEMISTRYWORLD.COM 

PODCAST TRANSCRIPT
Ben Valsler

Most of the potential Covid-19 treatments we’ve looked at on the Chemistry in its element podcast have been evaluated on their ability to treat severe disease – drugs that can prevent deaths, reduce time in intensive care or get people discharged from hospital sooner. And in the peak of a pandemic that certainly makes sense. But we’ve said little about drugs that treat milder cases – those that don’t necessitate a trip to hospital. New clinical trial data suggests that favipiravir, a drug licenced in Japan to treat influenza and also known as Avigan, may significantly reduce Covid symptoms and viral load in just a few days.



Source: © kitzcorner / Shutterstock.com
The night shopping area of Dotonbori, draws crowds of tourists visiting Osaka

Favipiravir seems to be effective against a wide range of viruses – including well known ones like influenza and norovirus, but also alphavirus, filovirus, arenavirus and the flaviviruses responsible for West Nile fever, Dengue, Zika and yellow fever. It works by preventing viruses from replicating through inhibiting RNA-dependent RNA polymerase – a similar mechanism to remdesivir. Taken orally, it’s what’s known as a prodrug – it’s metabolised into its active form once inside the body. It seems to have relatively few side effects with one major exception – it can cause significant defects to a developing embryo, so should be avoided by people who are pregnant or trying to become pregnant.

In the aftermath of the fatal H5N1 epidemic in Hong Kong in 1997, demand grew for medications that could treat new strains of influenza. A joint effort between Fujifilm’s Toyama Chemical Co, Hokuriku University and the University of Toyama screened 30,000 candidate molecules for biological activity, looking for antibacterial, anti-inflammatory, immunomodulatory and antiviral properties. One, a derivative of the tuberculosis medication pyrazinamide, known as T-705 compared favourably with established flu drug oseltamivir, which you might know as Tamiflu.




One big advantage of favipiravir is that it seems to be relatively difficult for viruses to become resistant. In lab studies that actively tried to develop resistant influenza, researchers struggled to evolve a virus that was both resistant to the drug and capable of enough reproduction to become the dominant virus type. There’s also no evidence of resistance developing during clinical trials – something that has been seen in trials of oseltamivir and other antivirals. That’s not to say it can’t happen, of course – mutations have been identified that offer protection against the drug, but at a cost. If another mutation can compensate for the loss in viral fitness, resistance could evolve. Life (or in this case an ‘organism on the edge of life’) finds a way.

It may come as a surprise, then, that favipirivir is not widely licenced for use against influenza. The risks in pregnancy may have been enough to cause most countries to stick to their existing flu provisions. Even in its home country of Japan, it’s licenced only as a treatment for novel or re-emerging strains of influenza, and not for the seasonal infection. That’s not to say it failed as a medication; In 2017, Japan created a stockpile of the drug – enough to treat 2 million people in the event of an influenza epidemic.



Source: © kitzcorner / Shutterstock.com
Face masks were common in populated areas of Japan prior to the Covid-19 pandemic…

In a pattern that is probably becoming familiar to covid-treatment-trackers and podcast listeners, favipiravir has also shown promise in treating Ebola. In 2014, a French volunteer nurse who contracted the disease in Liberia recovered after receiving favipirivir alongside other experimental treatments, but initial trials showing positive results in mild cases were criticised for poor experimental design.

Ebola, then, as was the case with remdesivir, leads us to Sars-CoV-2, the coronavirus responsible for Covid-19. Chinese clinical trials showed favipiravir to be ‘clearly effective’ – patients tested negative for the virus in an average of just four days, compared to 11 days for controls. Symptoms improved alongside reduced viral load, with lung function improving in 91% of patients on the drug, vs 62% of those without. In a Russian trial, body temperature in 68% of patients on favipiravir returned to normal in half the time of those in the control group. A trial in Japan, however, showed limited effect in people with higher viral load, suggesting it’s most likely to be of use in mild to moderate cases. Trials are also underway worldwide exploring the efficacy of favipiravir alone and in tandem with other drugs.



Source: © Ned Snowman / Shutterstock.com
…now even the shop mascots are wearing them.

The promising results so far have led to a spike in demand. Thailand has ordered 400,000 tablets from China and Japan, Germany is said to be purchasing millions. While companies in China, Russia, Bangladesh and India are amongst those producing their own supply of generic favipiravir, following fast-tracked approval.

It’s now been more than eight months since Covid-19 was first identified, over 17 million cases have been reported and nearly 2000 clinical trials undertaken worldwide. In that time we’ve seen the rise and fall of a number of promising treatments. Favipirivir is on the rise – will it be the next promising candidate to fall?

Next week, Mike Freemantle on gypsum, and a fantastic discovery in Mexico.

Mike Freemantle

One of the geologists who subsequently visited to research the cave described it as ‘the Sistine Chapel of crystals’. The crystals were up to a dozen metres long, four metres wide, and 55 tons in weight. They are thought to be the largest natural crystals in the world.

Ben Valsler

Join Mike next time, and many thanks to Jeff Silver for suggesting we take a look at favipirivir – Jeff certainly seems to have demonstrated some foresight when he got in touch back in April. If you would like to suggest any compounds for us to cover – email chemistryworld@rsc.org or tweet @chemistryworld. And you can find all of our previous pods at chemistryworld.com/podcasts. I’m Ben Valsler, thanks for joining me.

Additional information

Theme: Opifex by Isaac Joel, via Soundstripe

Additional music: Serene Waters by Aeroplanes and Cherry Blossom by Simple Thieves, via Soundstripe

UPDATES TOO
Encouraging signs from initial Covid-19 vaccine trials
BY ANTHONY KING11 AUGUST 2020

There’s been a surge of data emerging from Covid-19 vaccine trials. The studies are mostly Phase 1 safety trials, but can give some hints of immune response to the vaccines. At the same time, trials in which animals are immunised and then deliberately exposed to the virus give positive indications of potential protection. However, we still don’t know what level of immune response will be protective for humans, nor how long that protection will last.



Source: © Felix Dlangamandla/Beeld/Gallo Images/Getty Images

As initial data shows the vaccines are safe and elicit positive immune responses, companies are racing to start larger trials in areas where the virus is most prevalent to determine its efficacy

The acknowledged leader is the candidate from the University of Oxford, UK, which is a chimp adenovirus vector (ChAdOx1) expressing the entire spike protein of Sars-CoV-2. A randomised controlled trial of over 1000 healthy adults showed an encouraging antibody and T cell response.1 The vaccine is to be manufactured by AstraZeneca.

‘Both arms of the immune system were very well stimulated, including a very good T cell response,’ says Adrian Hill, director of Oxford’s Jenner Institute. The immune response, especially in terms of neutralising antibodies, was significantly increased by a second dose. That will be influential in planning future trials and any eventual rollout, Hill confirms.


The big question is how strong an immune response you need to induce protection

ADRIAN HILL, UNIVERSITY OF OXFORD

The levels of antibodies or T cells needed for protection are as yet undetermined, points out Dennis Burton, an immunologist at the Scripps Research Institute in La Jolla, US. ‘That is the acid test for any vaccine,’ he says. It’s likely that T cells in particular will be important for long-term protection.

China’s CanSino Biologics reported results on the same day as Oxford from a study that administered two different doses of its adenovirus-type 5 (Ad5) vectored vaccine in a trial of 600 volunteers in Wuhan.2 Ad5 is relatively common in humans, and 52% of the trial participants already showed antibodies against it, but levels of Ad5 immunity will vary in different populations. People with high existing antibody levels to Ad5 produced around half as many antibodies to Sars-CoV-2. The T cell response was similar in those with and without pre-existing antibodies to Ad5.

The only other adenoviral vaccine on the market in Europe is for Ebola, approved on 1 July 2020. Scientists in Europe and the US have given Ad5 a wide berth, since an experimental HIV vaccine, developed by Merck & Co, appeared to increase rates of HIV infection. ‘The Chinese and Russians clearly did not believe [the data]. For the 2014 Ebola outbreak, they made Ad5 vaccines and both got licensed in their respective countries,’ says Hill.

Moderna, Pfizer, Sinovac

Also in July, Moderna finally reported full data from the Phase 1 trial of its mRNA vaccine.3 Researchers have expressed annoyance at the company’s tendency to press release headline results, rather than publish full datasets. Moderna has ‘dribbled out small amounts of data over time, which is frustrating and unhelpful,’ says Gregory Poland, director of vaccines research at the Mayo Clinic in Minnesota, US.

Its trial of 45 healthy adults tested two vaccinations of mRNA encoding the spike protein, 28 days apart. Binding antibodies to the spike protein increased rapidly after the first vaccination, and again with the second dose. Moderna is to begin a Phase 3 trial with the US National Institutes of Health, involving approximately 30,000 volunteers.

More than half of Moderna’s volunteers experienced minor side effects such as fever, chills, fatigue, headache and pain at the injection site. This is relatively common with vaccination. For the Oxford group, there were enough fevers and systemic side effects that the trial protocol was modified to include paracetamol before vaccination.

Earlier in July, Pfizer and BioNTech reported on their mRNA vaccine candidate, which encodes the receptor binding domain of the spike protein, encapsulated in a lipid nanoparticle. The preprint described a robust T cell and a strong antibody response4 in 60 participants in Germany who received either one or two doses. Since then, the companies have announced that a different vaccine candidate, which encodes the entire spike protein, is to start a Phase 2/3 study.

‘The caution here is that these vaccine platforms have never been licensed before in humans,’ notes Poland. In a larger trial with 20,000 people receiving active vaccine, a serious side effect that occurs in one in ten thousand people might be missed, he warns. Regulators will have to decide what compromises and level of risk is acceptable.


The fact a vaccine induces an immune response is not proof that it will prevent infection

GREGORY POLAND, MAYO CLINIC

Sinopharm and Sinovac’s inactivated virus candidate is also advancing to Phase 3 trials. It will be given to over 8000 healthcare workers in China, as well as trials in the United Arab Emirates and Brazil. ‘This is super old technology, and it is often hard to grow the virus, which is why rabies vaccine is so expensive,’ says Hill. For some, this brings advantages. ‘We know how to deal with the inactivated approaches,’ says Florian Krammer, immunologist at the Icahn School of Medicine in New York City, US. ‘We don’t have a single RNA vaccine on the market.’

This strategy tends to require two or three vaccine doses, and often an adjuvant such as alum to bolster the response. ‘[The World Health Organization is] not so keen on those vaccines,’ says Hill. This is mainly because when vaccines for Sars were tested in animals, there was some evidence of antibody-dependent enhancement – in which exposure after vaccination can lead to more severe disease. ‘I don’t think this is a major concern at this point,’ says Burton of the Covid-19 candidates.
Up to the challenge?

Early vaccine trial reports prompted a rash of optimistic headlines. ‘The big question is how strong an immune response you need to induce protection,’ says Oxford’s Hill. ‘Most people [are focusing on] neutralising antibodies, because they don’t induce high levels of T cells, but we do.’ Nonetheless, the responses from different aspects of the immune system necessary for protection remain unclear.

‘The major concern remains efficacy, and the durability of efficacy, which is why these Phase 3 trials will be so critical,’ says Poland. ‘The fact a vaccine induces an immune response is not proof that it will prevent infection. Many companies have got to this point and failed in Phase 3 trials.’ In the case of Ebola, inducing small amounts of antibodies with vaccine was enough to provide protection. Whereas even the highest antibody levels to malaria do not offer a strong defence on their own.

I was quietly pleased. The vaccines did what they said on the tin. So far, so good

DANNY ALTMANN, IMPERIAL COLLEGE LONDON

To try and get a handle on how these immune responses might translate into protection, researchers are conducting challenge studies. These involve animals – in this case mostly primates – being either infected or vaccinated and then deliberately exposed to the virus. One such trial, led by Dan Barouch at Harvard University, US, in May showed that macaques challenged with Sars-CoV-2 five weeks after an initial infection displayed strong resistance to the virus.5 A second paper revealed that macaques given a series of DNA vaccine candidates also appeared to have good protection when challenged with the virus.6 ‘We are trying to race into vaccines [for Covid-19], but we haven’t got a clue what the correlates of protection are,’ says Danny Altmann, an immunologist at Imperial College London, UK. Animal studies can provide some insights into where that bar lies.

Challenge trials in macaques conducted by Janssen,7 Oxford,8 Moderna,9 Sinopharm–Sinovac10 and Inovio11 have all produced some level of protection, although the precise details vary. ‘There are half a dozen groups trying to zoom into Phase 3 trials where the stakes and costs are high,’ notes Altmann. He says the animal data support all the vaccines as plausible candidates. ‘I was quietly pleased. The vaccines did what they said on the tin. So far, so good,’ says Altmann. ‘The Oxford one stands out in the rip-roaring levels of T cell immunity that they showed,’ he adds.
Lasting protection

With the coronaviruses that cause the common cold, immunity starts to wane around 80 days after infection. Burton, however, argues this is irrelevant. ‘They are two separate things,’ he says. ‘A vaccine can do a lot better than a natural infection.’ Burton describes the early results from the mRNA vaccines as promising. We can make guesses as to how long the response will last, he says, ‘but you have to put the vaccine into people to understand what happens in a larger population’. The spectrum of possible outcomes include preventing transmission entirely, preventing infection or just preventing an infection from developing into the disease. ‘If we had a vaccine that could prevent the disease in large numbers of people, that would be very welcome,’ says Burton.

Results from the Oxford­–AstraZeneca Phase 3 trials in the US, Brazil and South Africa could be available by September–October if all goes well. With five other candidates also already in Phase 3 trials, Burton believes that efficacy data for several vaccines will become available before the end of 2020, but warns against predictions. ‘In this whole pandemic, a lot of things have been done faster than one would have imagined even six months ago,’ he says. ‘But this is a new pathogen and nature may have lots of surprises along the way.’

References

1. P M Folegatti et al, Lancet, 2020, DOI: 10.1016/S0140-6736(20)31604-4

2. F-C Zhu et al, Lancet, 2020, DOI: 10.1016/S0140-6736(20)31605-6

3. L A Jackson et al, N. Engl. J. Med., 2020, DOI: 10.1056/NEJMoa2022483

4. U Sahin et al, medRxiv, 2020, DOI: 10.1101/2020.07.17.20140533

5. A Chandrashekar et al, Science, 2020, DOI: 10.1126/science.abc4776

6. J Yu et al, Science, 2020, DOI: 10.1126/science.abc6284

7. N B Mercado et al, Nature, 2020, DOI: 10.1038/s41586-020-2607-z

8. N van Doremalen et al, Nature, 2020, DOI: 10.1038/s41586-020-2608-y

9. K S Corbett et al, N. Engl. J. Med., 2020, DOI: 10.1056/NEJMoa2024671

10. Q Gao, Science, 2020, DOI: 10.1126/science.abc1932

11. A Patel et al, bioRxiv, 2020, DOI: 10.1101/2020.07.28.225649

A coronavirus vaccine is on the horizon, thanks to a key discovery by these researchers

by Lara Korte

Credit: Pixabay/CC0 Public Domain

When the latest coronavirus emerged, Jason McLellan and his team were ready to take action.

McLellan, an associate professor of molecular biosciences at the University of Texas, has been studying respiratory diseases for years. In 2017, McLellan's postdoctoral researcher Nianshuang Wang identified genetic mutations necessary to stabilize a key component of diseases like MERS, also a coronavirus.

So when Chinese researchers shared the genetic sequence of the new coronavirus on Jan. 10, UT researchers were able to quickly map the virus and inject it with previously-discovered mutations, allowing the researchers to freeze a key protein in a way that would become essential for creating a vaccine.

"Now every pretty much everybody's using them," McLellan said. "I think four of the five leading coronavirus vaccines all contain the stabilizing proteins my lab designed."

Several major companies, bankrolled by billions of dollars from the federal government, are in a race to complete clinical trials for their version of a coronavirus vaccine. It can normally take years for a vaccine to pass through clinical tests before it becomes available to the public, but the process has been expedited over the past several months for coronavirus vaccine candidates from companies including Pfizer, Johnson & Johnson, Novavax and Moderna.

The vaccine candidates are either in or close to the final stages of clinical trials before final authorization by federal drug authorities, and all four are using the UT team's discovery in their vaccine formulas.

"It's really exciting," McLellan said. "It's like everything I hoped for when I wanted to start doing research."

The success of the UT team's discovery hinges on the ability to map and identify what McLellan called the "Achilles' heel" of the coronavirus—the protein spike. This protein is the part of the virus that fuses onto healthy cells and transmits the infection. Researchers used mutations from earlier research to freeze the protein in its pre-fusion form. By putting a pre-fusion version of the protein into a vaccine, a person's immune system is trained to identify the virus before it latches onto cells, and create antibodies to fight it off.

"Antibodies need to recognize elements that are on the outside of the virus because they can't get inside of the virus," McLellan said. "So the spike is this massive entity on the outside of the virus, and it needs the spike in order to attach and fuse to cells, and if you stop either of those, you stop viral entry."

The researchers designed the necessary mutations within about a day of receiving the coronavirus genome. The McLellan lab completed the atomic-level structure, and graduate student Daniel Wrapp harvested and purified the spike protein.

Researchers at the National Institute of Allergy and Infectious Diseases, who are working on the Moderna vaccine, published the results of their Phase 1 trials with mice on Wednesday. The paper reported that the use of McLellan's stabilized spike protein elicited a positive immune response and prevented coronavirus infections in the lungs and noses of mice.

Moderna began its crucial Phase 3 testing late last month and plans to include 30,000 subjects from 89 centers around the U.S. It could be several months before the results of the study are clear.

A spokesman for the university said researchers so far have not received any payment for the use of their research in vaccine candidates. However, UT and the scientists may eventually see monies from licensing and royalties. The details are still being worked out between the university, the National Institute of Health and the drug companies, the spokesman said.

Meanwhile, the federal government is investing in mass production capabilities, with the hopes that one of the vaccine candidates will be viable by the end of the year. Last month, President Donald Trump announced a $265 million deal to secure manufacturing resources at a plant in College Station for the Novavax vaccine candidate. If Novavax makes it through clinical trials, the majority of its doses will be produced in Texas.

©2020 Austin American-Statesman, Texas
Distributed by Tribune Content Agency, LLC.

UPDATES

Russian vaccine launch shocks scientists
Sputnik V to be approved without large human trial data

 BY ANTHONY KING 14 AUGUST 2020 CHEMISTRYWORLD.COM

Russia’s unexpected authorisation of a largely untested Covid-19 vaccine has shocked researchers. Full scale production of the vaccine is to begin in September, with initial doses going to healthcare workers and vulnerable populations, followed by national rollout in January 2021.

The vaccine, developed at the Gamaleya Research Institute in Moscow, has apparently been tested on just 76 people. No data from animal or clinical studies have been published on potential efficacy or safety.



Russia coronavirus vaccine vials
Source: © Russian Health Ministry/Handout/Anadolu Agency/Getty Images

Rolling out the Sputnik V vaccine without the normal trials is a spectacular gamble when it comes to both its effectiveness at preventing the disease, and its potential for side effects

This is in stark contrast to even the most accelerated clinical programmes for other vaccines, in which phase 3 trials will recruit tens of thousands of volunteers to try and establish safety and effectiveness. Such large trials are also needed to spot uncommon side effects, which can quickly become a serious issue when a vaccine is given to millions of people. ‘Vaccine trials are harder to do in terms of safety and effectiveness because you must wait for people to get exposed,’ says epidemiologist Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins University, US. ‘It is really in phase 3 trials where you get a much better understanding of safety.’


Vaccines shouldn’t be the domain of Cold War political dispute

President Vladimir Putin’s televised announcement of the approval, dubbed Sputnik V, has an air of political point-scoring to it. ‘Putin says he will give it to other countries in October or November, which is just as we have our elections [in the US],’ says Hildegund Ertl, vaccine researcher at the Wistar Institute in Philadelphia,US, who is suspicious of this timing. ‘[Donald Trump] keeps saying we will have a vaccine by November.’ She hopes that the US and other countries will not tolerate political pressure on scientists to rush approval of vaccines. ‘Vaccines shouldn’t be the domain of Cold War political dispute,’ agrees Danny Altmann, immunologist at Imperial College London, UK. ‘This is incredibly unhealthy. The [potential] downsides are spectacular at every level.’

The Gamaleya vaccine trial used human adenoviruses to deliver RNA encoding the viral spike protein. The official website for Sputnik V describes its adenoviral vector technology as having been in development since the 1980s, with numerous studies showing effectiveness and safety. However, while Russia licensed vaccines using adenoviral vectors for Middle East Respiratory Syndrome (Mers) and Ebola, there were no large phase 3 studies for them. ‘Neither the adenovirus vectors nor the RNA vaccine have been licensed for any disease [in Western countries],’ notes Ertl. ‘Some have undergone large scale clinical trials, but we have zero experience in mass vaccinations.’

The Russian vaccine uses two different viral vectors, human adenovirus type 26 (Ad26) in an initial dose, and human adenovirus type 5 (Ad5) in a booster three weeks later. Both normally cause common colds, so a proportion of people will already have antibodies to them. That may lessen the vaccine’s effectiveness at stimulating an immune response against the Sars-CoV-2 virus. Ad26 is the same vector being employed by Johnson & Johnson (J&J), while China’s CanSino Biologics is using Ad5.

In principle, Ertl in principle likes the Russian approach of using two vectors. ‘It has a chance of being efficacious, and a reasonable chance of being safe. I just wish they would do a phase 3 trial like everyone else,’ she says. ‘It would take them another two or three months and then I would say great, wonderful job. But this way, I am just shaking my head, like every other scientist in this country.’

If the Russian gamble fails, it could damage public acceptance of other Covid-19 vaccines. ‘If there is a surprise, an adverse reaction which shows up once you inject 20,000 people, then people who wanted the vaccine will change their minds and we will never get a handle on this pandemic, until we have herd immunity in about 20 years,’ says Ertl. Such a failure could also impact acceptance of the vaccines that share the same vectors.

Salmon says he is not worried about European or US regulators pushing the limits in terms of vaccine safety, but has concerns about politicians who ‘don’t always appreciate the value of science’.

Anthony King

I am a freelance science journalist based in Dublin, Ireland. I cover a variety of topics in chemical and biological sciences, as well as science policy, health and innovation.

EU agrees first Oxford Covid-19 vaccine deal with AstraZeneca in WHO blow

A volunteer participates in the vaccine trial in Oxford, England (AP)

 Updated: 14 Aug 2020 Reuters

The deal included an option to purchase 100 million additional doses from the British drugmaker should its vaccine prove safe and effective
The EU said over the past two weeks it was in advanced talks with Johnson & Johnson and Sanofi for their vaccines under development

Brussels: The European Union has agreed to buy at least 300 million doses of AstraZeneca's potential COVID-19 vaccine in its first such advance purchase deal, which could weaken plans led by the World Health Organisation for a global approach.

The European Commission, which is negotiating on behalf of all 27 EU member states, said the deal included an option to purchase 100 million additional doses from the British drugmaker should its vaccine prove safe and effective.

The EU's bilateral deal mirrors moves by the United States and other wealthy states, some of which are critical of the WHO's initiative, and further reduces the potentially available stock in the race to secure effective COVID-19 vaccines.

The EU agreement follows an initial deal with AstraZeneca reached in June by Europe's Inclusive Vaccines Alliance (IVA), a group formed by France, Germany, Italy and the Netherlands to secure vaccine doses for all member states.

The Commission did not disclose the terms of the new deal and declined to say whether it had replaced the IVA's.

"This new agreement will give all EU member states the option to access the vaccine in an equitable manner at no profit during the pandemic," AstraZeneca said in a statement.

The EU executive said its deals are aimed at financing part of the upfront costs to develop vaccines. The funding would be partial down-payments to secure the shots, but actual purchases would be decided at a later stage by each EU state.

The EU said over the past two weeks it was in advanced talks with Johnson & Johnson and Sanofi for their vaccines under development.

It is also in talks with Pfizer , Moderna and CureVac to buy upfront their potential COVID-19 vaccines, EU officials told Reuters in July.

BLOW TO WHO?

The EU move could make more difficult efforts led by the WHO and GAVI, a global alliance for vaccines, to buy shots on behalf of rich and developing countries with a separate scheme.

The Commission has urged EU states to shun the WHO-led initiative because it sees it as too expensive and slow, EU officials told Reuters in July.

Now the Commission is openly saying that vaccines bought from AstraZeneca, and from other vaccine makers, could be donated to poorer states, effectively taking on the very task that the WHO is pursuing with the so-called ACT-Accelerator Hub.

Brussels has publicly said that its purchasing scheme is complementary to the WHO's, but in private told EU states that there may be legal issues if they joined the WHO programme.

Sex workers in India find new ways to earn amid coronavirus pandemic

Sex workers in India have had to adapt to new norms during the pandemic. While some have been doing temperature checks on clients and sanitizing their rooms after every visit, a few have turned to phone and internet sex.


When India entered its first lockdown on March 25 to contain the spread of the novel coronavirus, hundreds of thousands of sex workers across the country were cut off from their major source of income.

Even as help slowly trickled in, it was difficult for many of them to find a way to make ends meet.

"Until the end of June, there was no dhanda [a colloquial term meaning 'business'] for the sex workers. In Mumbai, the police vigilance was so strong that there was no activity in the brothels of Kamathipura," Priti Patkar, co-founder and director of the NGO Prerana Anti-Trafficking, Mumbai, told DW.

"While there was relief in the form of food grains and utilities, this did not help the women with their rent and debt payments," she said.

Read more: Street crime and cyberfraud are on the rise in India during the pandemic

Since the start of the pandemic, authorities have been providing aid in the form of essential food commodities to economically underprivileged citizens, including sex workers.

"However, the government only provides for those who are able to produce ration cards. More than 50% of sex workers across India do not have ration cards, or any such documentation," Smarajit Jana, chief adviser to the Durbar Mahila Samanwaya Committee, told DW.

The DMSC, which represents more than 65,000 sex workers, has been working to provide essential food items, sanitary napkins and other necessities to sex workers. The collective operates in Sonagachi, Kolkata, Asia's largest red-light district.

Adapting to the pandemic

With the lockdowns in place, sex workers found it almost impossible to work. As India began to loosen restrictions in May, activity returned to the red-light districts as well.

"We have been doing temperature checks and screening customers for symptoms when they enter the district. We also sanitize the room before and after the customers leave," Kajol Bose, a sex worker and the DMSC's secretary, told DW.

"Some of the higher-class-category sex workers have been able to earn with the use of phone and internet sex. But this is not an option for all of us," Bose said.

Read more: Is the Kerala model in India really working during the pandemic?

Prerana's Patkar said phone sex, though a better option in terms of physical distancing, may not be viable for the most vulnerable. "It is an option for those who cater to the middle- and high-income clientele," she said. "But lower-income sex workers do not have the necessary skills, space, and connections for this."

Alternate income sources

Patkar said a few sex workers had been able to find alternatives to their profession to earn a living. The NGO was able to organize grants for a few women to set up microbusinesses, such as stores for selling dry fish, onions and potatoes, or tea stalls.

The women of DMSC have been employed in making masks and sanitizers, which have been used by the community themselves. "In the coming days, we're also going to start producing PPE kits. As we increase our production, we are planning to sell all these items in the future," the DMSC adviser Jana said.

Sex workers are among the people most severely affected by the pandemic.

Food supplies and donations have not been able to supplement their needs. Many of them have been struggling to meet their financial needs, such as paying rent and school fees for their children.

"Some of them also had to face harassment and violence from their brothel keepers," Patkar said.

Read more: India's HIV and TB patients suffer consequences of coronavirus pandemic

Though many migrant workers and daily-wage laborers chose to go back to their hometowns, a lot of sex workers didn't have that option.

Sex workers face massive discrimination in the South Asian country, and there's a lot of social stigma attached to the profession. Sex workers are also often trafficked to big cities.

Cities such as Mumbai and Kolkata have the highest number of cases of women and child trafficking, according to the National Crime Records Bureau. "Going back to the village? That's not an option for me. I am not wanted there. I have to find another option for a livelihood. Give me any other job and ask me to learn anything," said Mira, from Mumbai's Kamathipura district.

The German company that enabled the Holocaust

Topf & Sons helped make the Holocaust possible by building incinerators for Nazi concentration camps. After the war, the owners saw themselves as victims, with only one family member standing up to take responsibility.


Auschwitz-Birkenau, Buchenwald, Dachau, Mauthausen: When Allied liberating forces arrived in Nazi concentration camps at the end of the Second World War they discovered piles of dead bodies and crematoria bearing the logo of J.A. Topf & Sons.

The infamous German company, based in the eastern city of Erfurt, had collaborated with the Nazis, designing, building and delivering equipment for the mass incineration of prisoners — a ghastly invention that made the Holocaust possible.

Read more: A German town and Josef Mengele, Auschwitz 'angel of death'

Success under the Nazis

The company, founded by Johannes Andreas Topf in 1878, initially specialized in constructing brewery equipment and exported its wares around the globe. Then, after the First World War, the owners discovered another business opportunity – building ovens for city crematoria. During the Weimar Republic Topf & Sons became a market leader in oven manufacturing known for its "optimal implementation of the commandments of piety."

The company's business continued to flourish after Adolf Hitler came to power. From July 1937 onward, both the company's bosses, Ludwig Topf and his brother Ernst Wolfgang – who had since joined the Nazi party – could see the Buchenwald concentration camp from their office windows.

Read more: 'I think it can happen again' — Holocaust survivor meets Merkel ahead of Auschwitz liberation anniversary

The SS orders its first ovens

Buchenwald would soon become the first camp to use the company's ovens, as the growing number of dead in the camp — through torture or starvation — posed a serious logistical problem for the SS troops operating it. This problem was compounded after Germany invaded Poland on September 1, 1939. At that point, the camp was faced with an enormous influx of prisoners, and masses of those prisoners were dying.

Company bosses Ludwig and Ernst Wolfgang Topf

Before the war had even begun, SS officers had already looked into the idea of erecting large crematoria on site. In May 1939, Kurt Prüfer, Topf & Sons' chief engineer, presented his first design for a "mobile, oil-fired Topf & Sons cremation oven."

"The incinerator marked a radical departure from the culture and the rules of cremation. Human beings were burnt in them like refuse," writes Annegret Schüle, curator of the memorial site on the grounds of the former factory.

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Collaboration reaches new heights

Prüfer was encouraged by the initial success of his design, and soon presented the Nazis with a new oven featuring two incineration chambers. That model was eventually installed in the Dachau concentration camp in November 1939. Thereafter, the ambitious engineer designed his first stationary crematorium. The company was so proud of its work that it applied for a patent on the design.

"Prüfer's attitude, exemplified by personal initiative with no moral qualms, was emblematic of the stance of those in the technical department," says Rüdiger Bender, chairman of the Society for the Promotion of the Topf & Sons Place of Remembrance. Bender emphasizes, however, that leading engineers at the company were not staunch Nazis.

"The company was never forced to build the ovens, quite the opposite in fact. Rather, it did its best to beat out competition from other companies, like Heinrich Kori in Berlin, which was also vying for the contract," says Annegret Schüle. She says engineers at Topf & Sons took the initiative and designed increasingly powerful ovens. The company was happy to oblige the regime, and a correspondence with the SS written on company letterhead documents as much, it reads: "Always a pleasure to do business with you."

The Topf & Sons headquarters in Erfurt, pictured in 1935

When Nazi leaders decided to make Auschwitz-Birkenau a central hub in the Holocaust, the oven manufacturer's complicity reached new heights. "When SS administrators at Auschwitz discovered they could kill thousands of people in minutes using Cyclone B (hydrogen cyanide), they were faced with the problem of disappearing the bodies," says Schüle. The answer was provided by Top & Sons' ovens.

On August 19, 1942, Prüfer met with SS construction managers. During the meeting it was decided that three massive crematoria would be needed on the site. Two more would later be added. By the summer of 1942, the Nazis were incinerating up to 9,000 bodies a day.

But Prüfer's success was a thorn in the side of his colleagues, and in September 1942, his boss, Fritz Sander, presented a new invention of his own: The multi-muffle oven. This new oven was designed to allow the uninterrupted cremation of bodies in a "production-line" system.

Read more: The Nazi archives: Where Germany's dark past is stored on paper

'Textbook example' of Holocaust complicity

Technicians from Erfurt, including fitter Heinrich Messing, were soon dispatched to Auschwitz to begin construction of the new design. They spent long periods of time at the camp and were well aware of the genocide taking place there.

Interestingly, Messing was a communist and a member of the Communist Party of Germany, or KPD. Still, his own beliefs did not keep him from conscientiously completing the job at Auschwitz ahead of schedule. "Theoretically, he could have sabotaged the project, or at least delayed completion. But he didn't," says Rüdiger Bender.

Today, the site of the former Topf & Sons headquarters has been turned into a memorial

Annegret Schüle writes, "In the early 1940s, technology designed for the incineration of human beings and the disposal of bodies only accounted for about 2% of J.A. Topf & Sons' annual profits." Still, she says, the company is a "textbook example of how companies were complicit in the Holocaust."

Read more: Retracing Germany's tragic Kindertransport, 80 years later

One boss commits suicide, the other flees

When Nazi Germany was defeated in May 1945, Ludwig Topf committed suicide by swallowing a cyanide capsule after he was informed of his pending arrest by US military officers. In a suicide note, he defiantly declared his innocence, writing: "… if the people want blood, I'll do it myself. I was always forthright — the opposite of a Nazi — everyone knows it."

His brother Ernst Wolfgang fled to the Western occupation zone, where he rebuilt the company, and investigations into his wartime activities were eventually closed. It wasn't until the publication of the book "Macht ohne Moral" (Power without Morals), written by concentration camp survivor Reimund Schnabel, that the West German public was reminded of the company's earlier activities. After that, Topf was no longer extended credit and the company soon went bankrupt.

Engineer Kurt Prüfer, meanwhile, died in a Soviet prison camp in 1952.

Topf & Sons' Nazi past was all but forgotten in East Germany after it was nationalized and its name changed to VEB Erfurt Malting and Storage Company, eventually going bankrupt in 1994. It was not until the fall of the Berlin Wall and an attempt by a Topf heir to gain restitution that the public became aware of the company's dark past.

Read more: Heiress downplays factory's forced labor use during Holocaust

Fighting to keep memory of Topf & Sons' history alive

That was when Hartmut Topf, a great-grandson of company founder J.A. Topf, got involved. The journalist decided to make it his life's work to research the company's history and preserve it for coming generations. "After the Wall fell, I saw a newspaper article about a West German woman seeking restitution from the city of Erfurt," says the 85-year-old.

Hartmut Topf has kept the memory of the company's history alive

"That set off alarm bells for me. I thought – wait a minute – if there is any money at all, it should be given to civic education programs or to victim compensation funds," he says.

Initially, politicians in Erfurt were less than enthusiastic about his plan to open a memorial site on the grounds of the former factory. But in the end, Topf and his associates won out, and a place of remembrance was opened on the site of the company's former administrative offices in 2011. There, a permanent exhibition illustrates the company's history.

Topf also faced prejudice when in Poland. Two years ago, when he mentioned his name at the Memorial and Museum Auschwitz-Birkenau, the elderly greeter at the entrance became irritated. "Your name does not have a very good reputation here," said the man. To which Topf replied, "I know, that's why I am here."

From the "Guilt without atonement" series, a project of DW's Polish department, the Interia portal and the Wirtualna Polska media group.

In the SS' Service: Female guards at Germany's Ravensbrück concentration camp

An exhibition in the memorial at Ravensbrück offers a disturbing look at life under the Nazis in the all-female camp.





Bad conscience? Regret? Maria Mandl did not remotely experience either of those. "There was nothing bad about the camp," said the senior overseer of the all-women's concentration camp in Ravensbrück, Germany. The 36-year-old was hanged in 1948 after a Krakow court sentenced her to death as a war criminal.

Her career of cruelty is part of the new exhibition about female concentration camp guards at the memorial site. Over 140,000 people, mainly women and children, from over 30 countries were imprisoned in Ravensbrück, 80 kilometers (50 miles) north of Berlin, between 1939 and 1945. The camp was also the main training and recruiting place for female guards. Some 3,300 of them worked in Ravensbrück.


German shepherds were used as guard dogs at the Ravensbrück camp

The Austrian Maria Mandl was exactly what the self-proclaimed proponents of the "master race" wanted their female guards to be: loyal and merciless.

Someone like Mandl could go places under the perverse hierarchy of the Nazis. In 1942, after three years in Ravensbrück, she was transferred to work at the death camp Auschwitz. There, she created the Women's Orchestra of Auschwitz that was forced to play music during prisoner transports and executions.

In 1940, after World War II had begun, the female guards became subsumed under Hitler's elite death squad the SS (Schutzstaffel, Protection Squadron in English.) The freshly designed and updated exhibition, "In the SS's Service," first conceived in 2004, does not shirk from details. The location of the exhibition was also carefully considered: The old barracks for female camp guards, right next to the former camp. Only a wall and barbed wire separated the perpetrators from their victims.

Read more: Auschwitz: A scene of atrocities even before the horrors of the Holocaust


Female guard Johanna Langefeld lived with her son at the camp

'You are a lady, but I can hit you'

Audio files of the torment and capricious abuse carried out on the prisoners can also be heard in the exhibition. Some of the interviews with witnesses are more than 20 years old. Ursula Winska from Poland, for example, explains in a video how Maria Mandl beat an older woman especially brutally on a pathway in the camp. When a fellow inmate came to her aid, she in turn ended up in the bunker. For months after, she was hit in the face every day, with the mocking comment: "You are a lady, but I can hit you."

There were some female guards who occasionally showed some humanity. According to another Polish prisoner, Henryka Stanecka, her group of prisoners were permitted a dip in the lake after finishing a muddy day's work in a sugar beet field. "One guard even gave us a towel," Stanecka said.

Read more: The German company that enabled the Holocaust

The main requirement to work at the camp was loyalty to the Nazi party
'Attractive as mindless assembly line work'

The longer the war went on, the more difficult it became for the Nazis to find volunteer guards. New staff were recruited through advertisements in newspapers. The words "concentration camp" did not feature in these job descriptions. For example, a 1944 advert in the Hannoverscher Kurier read: "Looking for healthy female workers aged 20-40 for a position in military service." Compensation was accorded based on tariffs for public servants. Furthermore, the role promised: "Free accommodation, catering and clothing (uniform)."

Prospects like this were enough for many women to volunteer. One woman identified only as Waltraut G. was among them. In a 2003 interview, she explained that she took the job for financial reasons. She was the oldest of five siblings. "So I really did not think about it for too long, all I thought was: If I can earn more there then I'll take the job." Anna G. also had no scruples in taking the job. She found the work in the camp quite simply "attractive as mindless assembly line work," like in a factory.

Read more: Auschwitz, 75 years later: A race against time

Only some went to trial

Apparently, only a very small number of the guards quit or expressed any kind of opposition. But exhibition curator Simone Erpel says "we have found no indication that anyone who quit or voiced any kind of opposition was persecuted in any way.

"That is important because after the war the guards said in their defense, that they would have been thrown into a concentration camp had they dared to refuse to follow orders, but we find no indication of that, so it must have been possible for them to make their own decisions," Erpel says.


Curator and historian Simone Erpel put the exhibition together

The majority of female camp guards had little to fear after the war. Only 77 of them had to stand trial, according to Erpel, who is also a historian. Death sentences, like in the case of Maria Mandl, or long prison sentences were rare. Later investigations were mostly without consequence for those geriatric female camp guards who were still alive. Most recently, proceedings in eight cases were officially closed in February 2020 by the German state of Brandenburg, where Ravensbrück is located: seven because the defendants were unable to be questioned or attend hearings and one because of a lack of sufficient evidence.

Read more: Germans want to uphold culture of Holocaust remembrance

Some female guards were put in US prisoner of war camps in 1945

A genuine Nazi uniform?

"Not guilty" — that's how the few female guards whose cases did make it to trial pleaded. As far as the perpetrators were concerned, that was all that needed to be said. None said anything that could have helped their victims at all. This chapter of German case law is now "history" — 75 years after the liberation of the Ravensbrück camp — according to one state prosecutor, in an interview that can be heard at the exhibition.

There is also a room which deals with "Facts and Fiction." This looks at the figure of the female camp guard in literature and film, along with the trade in Nazi memorabilia. Next to the novel The Reader by Bernhard Schlink, which has been translated into 50 languages and made into a movie with Kate Winslet, you can see a field-gray SS uniform. "It could be a fake," the accompanying text reads, explaining the uncertain origin of the piece of clothing — but there is a female guard's cap that is definitely real. It was given to the Ravensbrück museum by a former French prisoner.

Doll in SS uniform

A doll in an SS uniform

Around the final corner of the exhibition you can find a glass cabinet with a doll in it. Her name is Silken Floss and she is an action figure based on the main character in Frank Miller's 2008 movie The Spirit. Scarlett Johansson plays the hero in a tale based on a comic strip by Will Eisner from the 1940s and '50s. The original comic is a crime thriller with mystical and comedic elements. The doll in the memorial at Ravensbrück has blonde hair and wears an SS uniform. You can buy things like this very easily online — but you might also find that in bad taste.

 I HAVE ALWAYS BEEN A BIG FAN OF THE SPIRIT COMICS AND WILL EISNER 

Silken Floss | Tranquil Tirades Wiki | Fandom

https://tranquiltirades.fandom.com › wiki › Silken_Floss

Silken Floss is an antagonist in the 2008 film, The Spirit. She is played by Scarlett Johansson...

Silken Floss | DC Movies Wiki | Fandom

https://dcmovies.fandom.com › wiki › Silken_Floss

Silken Floss is the Octopus' assistant.

The Spirit (2008) - Scarlett Johansson as Silken Floss - IMDb

https://www.imdb.com › title › characters

Quotes · Silken Floss : We knew there had to be a better way of keeping someone alive other than cutting them up like some free-range chicken. · [On the Subject of ...

The Spirit (film) - Wikipedia

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In a secret lair, the Octopus and Silken Floss discover their chest contains the Golden Fleece, not the Blood of Heracles, as expected. Sand and Mahmoud visit ...

‎Plot · ‎Cast · ‎Production · ‎Reception

Silken Floss (Character) - Comic Vine

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For the live-action adaptation directed by Frank Miller, Silken Floss is the Spirit's enemy, and the Octopus' secretary. She is portrayed by actress Scarlett ...

Scarlett Johansson portrays Silken Floss in The Spirit.

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Scarlett Johansson portrays Silken Floss in The Spirit. 07.23.2014. Scarlett Johansson portrays Silken Floss in The Spirit. Scarlett Johansson portrays Silken ...

Silken Floss rewritten for Scarlett Johansson

https://www.smh.com.au › entertainment › silken-floss-rewritten-for-scarlett-...

Dec 9, 2008 - Director Frank Miller has revealed he rewrote the role of Silken Floss in his upcoming film The Spirit to capitalise on Scarlett Johansson's ...