Transmission electron microscope image of SARS-CoV-2. Image from NIH.
Antivirals have several advantages over vaccines. They tend to be broadly effective against viral variants and offer faster-acting protection than vaccines. In addition, antivirals are usually simple to transport and don’t require ultra-cold storage. And oral antivirals would have an advantage in terms of the speed of protection they offer. For SARS-CoV-2, antivirals also could provide an alternative to vaccines in the scores of vaccine-hesitant people. Additionally, antivirals have a proven track record against other viruses like HIV and hepatitis C, where vaccines aren’t available.
“We need antivirals,” surmised Kamlendra Singh, a molecular microbiology and immunology professor at the University of Missouri (Columbia, Missouri).
“It’s not that the vaccines aren’t working. They are working wonders,” Singh said. But antivirals will likely emerge as an indispensable tool as SARS-CoV-2 continues to mutate, Singh said.
Antivirals can limit the multiplication of virus in the body, leading to milder illness. They also could potentially inhibit transmission.
Already, the Delta variant has served to stress-test the currently available vaccines, which remain effective but less so than against earlier variants. The Delta variant is presently responsible for 99% of COVID-19 infections, according to the CDC. It has also caused significant surges in disease in India, Israel, the U.K. and U.S.
“I don’t think Delta will be the last [wave], Singh said.
The spread of HIV in past decades may provide some indication of what to anticipate from SARS-CoV-2. “People learn from experience,” Singh said. And researchers have substantial experience studying HIV.
Although HIV is a lentivirus (a genus of retrovirus) and SARS-CoV-2 is a coronavirus, both viruses encode their genome in RNA and mutate relatively quickly. While HIV mutates faster than SARS-CoV-2, the novel coronavirus mutates at least 50% faster than researchers anticipated, according to researchers at the University of Bath.
There are now hundreds of variants of HIV, which are known as circulating recombinant forms. “If HIV can mutate that much and still have structural integrity, I don’t see why coronavirus could not do that,” Singh said.
And yet, antiretroviral therapy has transformed the treatment landscape for HIV, leading to substantial improvements in morbidity and mortality.
But while a number of scientists and companies are working on antivirals for SARS-CoV-2, it may be too early to tell which will find broad use.
Merck and Ridgeback Biotherapeutics, Pfizer, Roche and Atea, Pardes Biosciences and university scientists are all developing antivirals for the pandemic.
An interim analysis from 775 patients enrolled in the Phase 3 MOVe-OUT study of Merck’s and Ridgeback’s molnupiravir found the drug cut the risk of hospitalization or death by approximately 50%.
While data to date have been promising, “we need more data involving thousands of patients” to evaluate the potential of a given antiviral, Singh said. “But I definitely think that the discovery of antivirals is very important,” he concluded.