To Win the Fight against COVID-19 in the Future, How To Make a Breakthrough in the R&D of New Drug?

Recently, with the continuous evolution and spread of Novel Coronavirus variant (including Delta-related variant viruses) all over the world, the mortality rate in some areas has a tendency to increase. Therefore, people's demand for specific drugs of COVID-19 is becoming more and more urgent. 

Remdesivir, once a magic medicine, has no longer been in use. 

Although Remdesivir showed unique curative effect on COVID-19 in early clinical research, it has now no longer been in use. Remdesivir, though, has shown efficacy in some mild patients and prophylactic medications. However, in severe patients, clinical researches have shown that no significant curative effect has been achieved by Remdesivir no matter in what type of severe COVID-19 patients. Therefore, Remdesivir is no longer recommended among severe COVID-19 patients. Even the World Health Organization has publicly prohibited the use of Remdesivir. At present, the best effect of Remdesivir is only to slightly shorten the recovery period of some patients. Moreover, related researches have also shown that it has some toxicity to liver and kidney. 

Monupiravir, Merck's COVID-19 oral medicine, remains to be discussed. 

Monupiravir, Merck's oral medicine for COVID-19,  is very popular in the market. As a specific drug of COVID-19, Monupiravir, in its promotion, mainly claims to make the viruses inside body drop sharply basically without any side effects if taking it for 5-8 days once infected with SARS-CoV-2. Therefore, it is highly promoted in the market and was once regarded as a new hope to overcome COVID-19. 

There will be some difficulties in the future for Pfizer's new drug, Palovid. 

Pfizer's anti-SARS-CoV-2 new drug is actually a protease inhibitor. Protease inhibitors are actually not specialized for specific viruses, such as SARS-CoV-2. Therefore, Palovid is actually a broad-spectrum antiviral drug. The target of Palovid is protease, and basically, all antiviral drugs, especially most of those anti-HIV ones, are used to inhibit protease. So Palovid, as a broad-spectrum drug, may only alleviate the symptoms of the infection of SARS-CoV-2, instead of completely curing or killing the virus. Its ultimate efficiency is limited.

Conventional drug in new use - Ivermectin from India 

Why reapply this conventional drug, Ivermectin in treatment? In fact, Ivermectin is a classic antibiotic. When the pandemic was spread in India, Ivermectin became the only available, cheap and widely popularized drug for ordinary Indians to fight against COVID-19. Therefore, some researchers believe that Ivermectin may have certain anti-SARS-Cov-2 potential. 

However, as the conventional drug, the patent of Ivermectin has already run out long ago. So basically, no company or researcher will be willing to try this conventional drug in new SARS-CoV-2 infected patients in the future. In other words, it can be predicted that the future clinical research of Ivermectin will lack high-quality evidence and data support, and the company will not invest in such clinical research. There will be a lack of support in the future. Therefore, the actual efficacy of Ivermectin to SARS-CoV-2 may always be a mystery. 

Can neutralizing antibody drugs become saviors? 

I mentioned a lot of small-molecule drugs above, but the result of the R&D of them against COVID-19 drugs is not likely to be ideal. Like other antiviral drugs, they are likely to have miraculous effects only in the first few days of infection. But if drugs are not used within a week after the development of symptoms, or if drugs are used in severe patients, it is too late at this time to take any small-molecule antiviral drugs. 

Usually when hospitalizing, the use of neutralizing antibody drugs is the best choice. Neutralizing antibody drugs first showed its efficacy in the treatment for former U.S. President Donald Trump. At that time, he used drugs including Remdesivir, neutralizing antibody and steroid hormones. Finally a very good curative effect has been acheived. It is said that neutralizing antibody played a main role. Whether neutralizing antibody drugs can become saviors of COVID-19 or not? Considering its cost, neutralizing antibody can only be available for a few people. 

COVID-19 vaccine is very beneficial, but the factor lies in the speed and cost. 

Vaccines are a solid firewall to prevent any virus infection. However, the update of vaccines often fails in keeping up with the speed of virus mutation. It was observed in the vaccine treatment of influenza virus. The general situation is that there is a new influenza virus subspecies prevalent, but the vaccine at our hands is the one for the virus that spread last year. Although it may work a little to get the vaccine of last year at this time, it is still too late and too costly. Therefore, mRNA vaccines which are similar to small-molecule drugs may become the leader of preventing COVID-19 in the future due to their easiness to be industrially produced on a large scale. 

Summary 

Nowadays, drugs against COVID-19 include small-molecule drugs, antibodies, vaccines and others. Why active efforts are still made in the R&D of small-molecule drugs? Because small-molecule drugs are very easy to mass-produce, and cost very little to store. With the 24-hour mechanized production of the global chemical industry, if there is a suitable specific small-molecule drug that can cure COVID-19 infection, it can be widely promoted to every corner of the world, thus ending the pandemic. But for now, there is still a long way to go.