 Satyajit, good to have you with us on NewsClick. We're going to discuss some of the issues which today are really making people rather worried about the future of the COVID-19 pandemic. So I'm not going to discuss specifically the Indian scenario, that we will reserve for another day. But broadly, when we look at the COVID-19 pandemic, the two questions that come to mind is that is there a quick solution we are going to get, either in terms of prophylactic or in terms of a treatment? And the second is of course, that when are we going to get the vaccine? So these are two questions I'm going to give, discuss with you. First is the question of the prophylactic curative part of it, which I think has a shorter timeline, if we can get it? Yeah. Keep in mind that a vaccine itself is of course the best prophylactic. Of course. That's it. If one leaves out the vaccine for the moment from prophylaxis, then what one is talking about is the kind of drug prophylaxis and the example that everybody is hyping currently based on our experience with malaria is of course chloroquine. And the famous British drinking gin and tonic. You would need a very, very substantial quantity, shall we say politely, of a multitude of gin and tonics every day in order to get the dose that you need. But that apart, there are three issues because of which people are talking about chloroquine or hydroxychloroquine prophylaxis. One is that as I said, we have some experience with chloroquine prophylaxis in malaria. So we are used to thinking about chloroquine in a drug based prophylactic arrangement. The second is that chloroquine is known to be an odd molecule that works on a wide variety of biological processes. And one of those happens to be broadly related to inflammation. And you will remember that chloroquine is used at least in some efforts to limit the symptoms of immune inflammatory diseases like rheumatoid arthritis. And the basis for that seems to be that it has some sort of anti-inflammatory activity to put it very broadly. There are speculations about how it works, although there's no really hard proof of how it works in those situations. And the third has come about because people have been trying drug repurposing for antiviral effects in a variety of contexts ever since the first of the three major coronavirus family outbreaks began close on 20 years ago, which is with what we used to call then as the SARS coronavirus or SARS-CoV and now we have begun to call SARS-CoV-1. And there was some evidence that when you took a situation where you took human cells, you put the SARS coronavirus onto human cells. It grew and you could stop that growth with a whole range of repurposable drugs that included chloroquine. And it's on that basis that people over the last two months, three months have been trying chloroquine for those sorts of tests. And it is as a result of that usage that the clinical use of chloroquine in patients has been attempted and reported. And you will note that I'm not using the face clinical trials because there has been no proper clinical trial of chloroquine. Simply clinical usage has been reported. The thing to remember is that typically in order to work well as a drug with a defined test tube efficacy, the potency of a drug has to be pretty high. The potency of chloroquine for SARS-CoV-2, which is our current epidemic virus, it's not very high, the reported potency. We can get into the technicalities of just how much, but the reality is, it's not very high. So it's not the viral property that could help in this case, but it could be the anti-inflammatory property. We don't know. Now, let me press that further. There are two separate time windows during the infection of an individual with SARS-CoV-2 in which we can intervene. The first is very early during infection. And what we would like early during infection is for the relatively limited virus load to be rapidly eliminated. And it's in that situation that you would like an antiviral effect, either a direct antiviral effect or an effect that increases the body's own antiviral inflammatory response. Excellent, so to say. So chloroquine's anti-direct antiviral effect may work at that point, but as I said, for that, the potency seems to be fairly low. On the other hand, we also want people who are in hospital with severe infections to be treated with something other than simply supportive therapy. And that's a situation in which chloroquine will have two separate effects, if at all it is affected. One effect will be the direct antiviral effect, but the other effect will be this more nebulous anti-inflammatory effect. And because people's lungs are being inflamed and affected, limiting the inflammation as well as controlling virus growth is useful. So keep in mind that what you are saying is that the SARS-CoV-2 has really these two phases, one in which you have a viral infection, that's a primary issue at that point. Later, when you get an inflammation of the lung, you could also have co-bacterial infection at that point. So at that point the regime might change because you need to address the issue of the bacterial infection, any other infection as well as take care of the inflammation of the lung, which is what is causing the seriousness of the pneumonia, which probably you are in at that point. That's absolutely correct. Those all become major contributing factors that need to be dealt with at that stage of the illness. And that is the ball critical hospital phase. That's right. And that's where the attempted usage of chloroquine has been made so far. The chloroquine has been from my seen trial that the trial or the use, the clinical use of the French case. So that's where we stand with chloroquine. In theory, one can wave one's hands and make all sorts of hopeful speculations. But in reality, there isn't really good basis for thinking about chloroquine prophylaxis as being a major factor. I may turn out to be wrong, but at the moment we certainly have no evidence to show that. Coming back to the antivirals, because what you're talking about before it goes to stage two, is there a quick antiviral that we can put into play? And some of the anti-AIDS drugs are being used in this context. It's also an anti-bola drug, which is Gilead's drug, which has also been used. And then also the part of the drug trials, interferon is also being used, interferon beta version is also being used. So all of these are to attempt to control the viral part of the infection. So in early during infection, there are two ways in which, as I said, we can attempt to help the body deal with the virus. One is to use direct antivirals. And I'll come to that in a second. The other is to increase the body's antiviral inflammatory response. The body has a number of different inflammatory responses. One of those categories is an antiviral inflammatory response. And one can increase the antiviral inflammatory response. So using a Gilead interferon alpha interferon beta, which is what you refer to, is that pathway. Talking about the direct antivirals, there are three categories of direct antivirals that are being thought about. One is, as I said, simply repurposing drugs, simply by taking a cell in tissue culture, putting virus, letting the virus infect the cells, and then trying every drug you have access to, to see if that drug interrupts every known already licensed drug, and seeing whether that drug stops or reduces virus growth in cells. And if it does, then that's a potential repurposible drug. And there are quite a few of these that we have already done. You also then short circuit the drug development process, because you don't have to do safety checks and all of that again. Correct. So there's already a longish list of such drugs that a number of labs across the world have developed. You will appreciate that this kind of research requires the test. You need cells growing in a test tube, and you need the actual infectious virus to put on the cells, which means you need infectious virus, which means you need the containment for the infectious virus. Now drug discovery against viruses has dealt with this problem for a long time, and one can use a viral mimic for this purpose. Last week, people have for the first time that I have seen reported such a viral mimic based test. And I'm hopeful they've said in their paper that they are willing to share these reagents widely. And therefore I'm hopeful that with that major efforts at both repurposing already licensed drugs as well as trying to find really potent new drugs can be done the world over from a wide variety of sources in a wide variety of public sector, public interest laboratories. So that's one source for antivirus. A second source for antivirus is as I said, this is not the first time that we've met the coronavirus family in a major disease outbreak. Both SARS and MERS, the so-called colonially named Middle Eastern respiratory virus, were coronaviruses. And people have been working on specifically drugs for them for quite some time. Some of those have gone through preclinical work as well as perhaps safely, human safety. So that's a second source because something that works against a related virus is likely to work against SARS-CoV-2. And the third is people are simply taking antivirus against all sorts of RNA viruses, since SARS-CoV-2 is an RNA virus and saying, let's see if it works. And the list amongst those is obviously the HIV and HIV drugs as well as others such as Zika and all sorts. The antibolar drug of Gilead. So those are the sources from where antivirals come. I'm not certain of just how well direct antivirals will work based on our experience with other effective antiviral drugs, immiral infections, direct antiviral drugs. So let me give you two examples. One is the example of Tamiflu, which those of us who have not remembered from 10 years ago. We are much older than that, not just 10 years back. So Tamiflu is a very important drug against antivirals and yet in the clinical setting it really needed to be given very early in order to limit the severity of illness. Second example that I can give you is that of acyclovir, which is a direct antiviral drug against herpes outbreaks, skin herpes outbreaks. Once again, unless you start the medication very, very early, as soon as symptoms varies, the drug doesn't, the drug is not, shall we say, the kind of magic bullet as an antiviral drug that effective antibiotics are against material infections. And that difference needs to be kept in mind when we decide what to expect even from effective direct antiviral drugs. There are reasons of differences in viral and bacterial biology for this, but broadly this is what we need to keep in mind. Coming back to the question that if we do get any of this work, even if it's a limited sense, which can bring down the severity of the infection, even that would be a bonus. It might stop along the hospital admissions and the seriousness of the case developing. So even that would really help. No question, but there are two major bottlenecks that we as as communities and when we think about public policy should keep in mind. One is the fact that this is epidemic and it's an epidemic where all of us across the world are potentially susceptible. And that means that the sheer demand per week on the amounts of a drug across the world is going to be monumental, which means that we need to fix, we need national level regulatory authorities to work rapidly to license these drugs, to give the permissions for usage of these drugs. And secondly, we need a manufacturing not just capability, but actual manufacturing to provide these drugs as medications at scale in the market. And those are not going to be trivial problems. They're not non-trivial, no question. But if we have a drug, then we can talk about how to manufacture it and how to scale it up. If we don't have it, of course, we go nowhere. And then depending on whether it's a small molecule or it's a complex, biologics, big molecule, of course, you have completely different scales of the problem. So scaling is a second issue that we would come to, but it would still be a happy problem to solve because it means we have something in the kitty at the moment. We don't really have anything in the kitty and that's the stage we are right in. So that's why the concern really is if we look at the future, that if we have at least some drug which would work even partially, it will make the possibility of treatment. And then it becomes really a manufacturing and a scaling issue. It moves beyond science into what I will call public policy, public health and your drug global infrastructure and the kind of global policies that will put in place. Coming back to the issue of, okay, what you've said is mixed. We have some hope, but lots of tests and maybe something will come out. Some, let's say some light maybe partially at the moment, but things are very, very uncertain in terms of the science that we are seeing. That's broadly the picture that we have. Some leads, but we have to really see whether the panel. Coming to the issue of vaccines, well is there a chance of getting a vaccine because you yourself just now said that vaccines are going to be the real issue? Is there a 12 months to 18 months is what is being said? Why to remember Swami Nathana, Swami Nathana saying at least one and a half months back that vaccines are 12 to 18 months away. The 12 months don't seem to move, but our timeline is continuously moving. Can't we say now it's over 10 to 14 months away? So there are, let me say something about the scientific difficulties, uncertainties about a vaccine, which also connects incidentally to therapeutics and that is at the moment we are not certain whether we make protective immune responses against SARS-CoV-2 and it's essential to know that before being certain that we can make a vaccine easily. Now, over the past 10 days, evidence has begun to come about some in humans at least one study in monkeys where it begins to appear that not only do we make immune responses to virus, that by itself is not surprising, but that immune response in the case of humans actually blocks the virus from infecting cells in a test tube, which is very useful information and in the monkeys. Let me break it down. Okay, so go ahead. Sorry, go ahead. In monkeys, it prevents them from being re-infected. Okay, now just to break it down for our audience, what you mean is that we at the moment do not know how much the protection extends after you are infected and you're cured. So you may be re-infected in one month, two months, three months, 12 months. This is the information we did not have earlier. Now we are starting to get some information. No? Okay. No. What we didn't know is whether we are protected at all. Okay. We now know that it's more than likely that we are. The question you're asking how is the next level question, how long are we protected? Okay. We still have no one. Okay. Okay. But quite frankly, from a vaccine point of view, the answer to the first question was critical and important. The answer to the duration question is not that critical. Think about it this way. Flu vaccines are seasonal vaccines. We take flu vaccines or more correctly, those of us who are fortunate enough in socioeconomic terms to have access to a flu vaccine, take flu vaccines annually. So it's not impossible for us to make do with a vaccine that provides for short-term protection because if we can vaccinate a sufficiently large fraction of the population, then we can break transmission cycles and we can keep transmission cycles under limits by limited vaccines. So what you're saying is that's why the first question is important rather than the second one. The duration would be if it lasts only 15 days, then we have to vaccinate every 15 days. That's unlikely from you. So that's extremely unlikely. It's a question of is it going to last for a few months or a few years? And that while important and interesting is not a legal break question for a vaccine. In terms of trying to stop the epidemic, it means that we have to vaccinate three times instead of once a year. That's what it would be what it amount to. And once you've broken the transmission cycle, we have controlled the pandemic. This is the basic message that you are giving. So some good developments right now, the four monkeys, macaques in China who are who underwent the test, the case that you were talking about. It's a preprint right now. And I don't know whether any other cases have been reported. Well, as I said, the human antibodies from people who have recovered seem to provide some indications of protection. So I think that the vaccine trials that have been accelerated, that are already in safety trials are in my judgment more than likely to succeed. So there's a whole range of vaccine designs that are already under trial. So there are two drug trials. One is a mRNA drug trial, which is being done by the Chinese and the other is the US mRNA trial, which is also listed by the WHO. And there is a German one which is supposed to come into quickly on stream again. Three trials that I can think of. There's also a vaccine designed in Oxford in the United Kingdom, which is on the work of entering trials. And there are two or three broad designs of vaccines that people are trying. One is to inject mRNA or DNA that codes for the viral proteins. But rather than making the protein and then injecting it into the body as a vaccine, the mRNA or DNA is directly injected into the body, allowing the body to make the viral proteins and to generate a new response against it. That's one category. The second category is to make the viral protein, the spike protein most commonly and to formulate it exactly like a tetanus vaccine and to inject that and generate any new response. A third, which again has been repurposed from a SARS vaccine, is to take another virus to put SARS-CoV-2 genes into that virus, so an adenomitis, and to use that as a vaccine. And all of these are under, I would say advanced preclinical development and likely to go into human clinical trials over the coming weeks rather than months. So, how fast can we crash the development cycle and ensure there will be safety or from the vaccine itself as well as efficacy? How long should it, can it now take given the scale of the pandemic and the fact that everybody is now concerned? So, my guess is that by the end of this calendar year, we will have clear evidence about at least one, if not more of these vaccine candidates, generating good stable immune responses that show markers of protection. How rapidly we can begin manufacture to a global scale, how quickly we can go through the regulatory processes that every country has of its own, become downstream manufacturing and policy issues, which the scientific and technological leadership is very low to predict. And in general, I suspect that that is why they are all being circumspect about how long it's going to take to have a vaccine in the marketplace. Again, I remind you of what happened with the SARS vaccine. With SARS, scientists and technologists began to develop a vaccine and had come through clinical studies, at which point it became apparent that it wasn't spreading enough for anybody to buy the vaccine. So, back the vaccines went onto the shelf and in fact, some of those have been dusted off and quickly re-engineered for SARS-CoV-2. So, in that sense, this is not going back to the shelves quickly because the scale at which this is spreading is very clear and we are not in the SARS control phase at all, SARS-CoV control, which globally we managed to do for whatever reasons it might be. The last question, I know that I've taken a lot of your time, the last question is the cycle since we are entering summer, even in the at least in the northern hemisphere. Do you think this is going to interrupt the cycle of transmission? Because it does seem to show the tropical areas are having a lower transmission. Frankly, I really don't know an answer to that question. I don't think anybody does. I don't think there is any reasonable evidence on which to base even a quasi-realistic guess. On that question, we just want to have to wait and raise ourselves and see the geographical, geoclimatic patterns that you're pointing to. At this point, could just as well be the swirling statistical probabilities that typically epidemics show? Or more closely following the travel patterns. If you're densely connected, this epidemic is likely to spread faster through those routes. Could be, you don't know. So what you're saying is just could be the artifact of the statistics rather than the real cause and effect that that's a possibility. Not much hope for the next 12 months that you're holding out, but maybe some improvements at least on the medical front in terms of repurposing drugs quickly. That seems to be our quickest bet. Let me put it this way. By the end of the year, we will have a number of effective ways. Okay. So in the long run, we are okay. The question is how to handle the short run, which is next nine months, not as long as Lord Cain's in the long run, we are dead, bottled. So only nine months will be a much better stage to give a definitive answer where we are. Thank you very much Satyajit for being with us and telling us all about the challenges that we face medically. We are not talking of socially, economically, none of these issues because that's a completely different ballgame altogether. And we will come back and discuss this another day. Thank you very much for being with us. This is all the time we have in NewsClick today. Do keep watching NewsClick and see our other programs.