New Covid-19 variant: Antivirals hold the key as mutations surface

With Omicron appearing on the scene as the new variant of concern, experts say developing antivirals is the way forward to combat Covid in the long run. If the ever-mutating virus keeps evading the vaccine-induced immunity, one can think of next-generation Covid vaccines, but it is antivirals that hold the key to combating the virus, say scientists.

Speaking to Business Standard, E Sreekumar, chief scientific officer at the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, explains that how a treatment works against new variants depends on which domains or parts of the spike protein have mutated.

“This one (Omicron) has over 30 mutations in the spike protein. Even though these are identified mutations, one has to see how significantly they change the protein; whether these mutations are in the regions that would affect the receptor binding. These things matter,” Sreekumar says.

He is of the view that monoclonal antibodies will not become completely useless and will have at least partial protection. But, he adds, “I don’t think monoclonal antibody treatment is the solution. We have antivirals that will target some of the viral replication stages, or key pathways used by the virus. Pfizer is coming out with some antiviral drug, and there are also others in the pipeline.”

Why are antivirals more likely to work?

Antivirals do not specifically target only the spike protein but the other parts of the virus, too.

Others like Shahid Jameel, senior research fellow at Green Templeton College at Oxford University, feel it is too early to say unless tests are done. “But there are several mutations in regions that are targeted by therapeutic monoclonal antibodies. There appear to be no critical mutations in the polymerase or protease regions that are targeted by the new Merck and Pfizer antiviral drugs,” Jameel says, raising hopes for antiviral drugs.

Pfizer has said that its Covid-19 antiviral drug used in combination with a widely employed HIV drug cuts the risk of hospitalisation or death by almost 89 per cent in high-risk adults who have been exposed to the virus. The drug is yet to be approved by any regulator.

Merck, on the other hand, has said recently that its molnupiravir showed a relative risk reduction of 30 per cent when compared with the placebo arm of the trial. Others like AstraZeneca are working on monoclonal antibody treatment, while Roche already has one such product in the market.

Jacob John, former head of the Centre for Advanced Research in Virology at the Indian Council of Medical Research (ICMR), too is of the view that antivirals will work. “Even vaccine-induced immunity will be useful. There can be breakthrough infections, but what matters is whether such cases are severe. We have seen that vaccines are working against various mutations, albeit with various degrees of efficacy,” he says.

Sreekumar agrees. He speaks of the Delta variant, which escaped immunity. “Even vaccinated people got infected. But, in those cases, the mortality was less. Even for this new variant, the vaccinated population will have an advantage for sure. I don’t see any new variant will turn into a third wave kind of a thing,” he says.

Speaking of treatments, Rahul Pandit, director-Critical Care, Fortis Hospitals Mumbai, and member of the National Covid-19 Task Force, says they were worried about the poor action of monoclonal antibodies. “From the current mutations, we are worried about an immune escape as well as poor action of the monoclonal antibody cocktail. We need to wait for some solid data before we start making such assumptions,” he says, adding that even to know if antivirals work, we need more studies.

The word of hope is that experts feel as viruses mutate, they typically tend to become less virulent but more transmissible. “In natural evolution, a virus gets adapted — maybe there will be more transmission, but it typically becomes less virulent. That is the way evolution drives the whole situation. If a virus becomes more and more virulent, it will kill the host and it cannot survive much longer,” Sreekumar explains.

While he thinks we don’t need to worry about this strain, he adds, “Like any other variant of concern, we have to wait and watch.”

Scientists say in the long run, we need to have more antivirals, and develop one specifically for coronavirus. “This will give us more confidence in dealing with the coronaviruses,” Sreekumar says. “For example, we have Tamiflu (Oseltamivir) for influenza. We also have vaccines. We are not very worried about influenza as we have the Tamiflu. We have a vaccine for Covid, but the next stage is to develop an antiviral.”