Among the coronaviruses known to infect humans, the clear winner at human transmission is the novel coronavirus, SARS-CoV-2, despite a lower mortality rate when compared to its more deadly cousins, SARS-CoV and MERS.
Since its discovery in the Chinese city of Wuhan in December 2019, numerous antiviral drugs have been tested for efficacy against SARS-CoV-2. At the time of publication, more than 400 clinical trials have been registered in ClinicalTrials.gov.
Providing a bird’s eye view of the current landscape, Justin Jang Hann Chu, a Joint Senior Principal Investigator at the A*STAR Institute of Molecular and Cell Biology (IMCB), and colleagues review the two main antiviral strategies currently in play—those that directly target the virus and those that indirectly target the cellular factors required for virus replication.
“Both antiviral strategies are promising,” said Chu. “Ideally, having a combination of an antiviral that targets both the virus and cellular factors required for virus replication could result in shorter treatment times, reduced emergence of drug resistance and fewer side effects,” he explained.
The first strategy—viral-directed therapies—targets the main viral replication processes in the coronavirus replication cycle. Drugs that fall into this group hinder viral entry into the host cell, or stop the virus from replicating itself. For example, viral genome replication inhibitors under testing include ribavirin, remdesivir and favipiravir.
“Drugs that target viral proteins or the viral replication process have been shown to exert good efficacy and be highly translational for clinical application,” said Chu. “Targeting the virus is straightforward and leads to fewer side effects. However, as SARS-CoV-2 is an RNA virus with a higher mutation rate, the emergence of drug resistant virus mutants remains a serious concern.”
In contrast, host-directed therapies indirectly target the virus by managing clinical symptoms of the disease. Through a myriad of ways, it is possible to enhance the innate immune response or reduce inflammation to fight the effects of the virus on the host. Candidate treatments include resveratrol, indomethacin and HIV-1 protease inhibitors such as nelfinavir and Iopinavir.
Describing the COVID-19 pandemic as one that will require “intense and sustained effort to control,” the authors are nonetheless optimistic that at least one of the 400 antiviral strategies in clinical trials will lead to its successful resolution, given the collaboration across academia, industry, governments and international organizations.
The A*STAR-affiliated researcher contributing to this research is from the A*STAR Institute of Molecular and Cell Biology (IMCB).
