Novel host-directed molecules blunt SARS-CoV-2, influenza virus

Novel host-directed molecules blunt SARS-CoV-2, influenza virus

Subject :Science and Technology

Section: Bio Technology

Context: Virus can develop resistance against antivirals, while drugs that target the host cells to prevent virus infection can remain effective even when the virus evolves.

More on the News:

• Indian researchers have, for the first time, been able to synthesise small molecules that can effectively halt the infection of cells by SARS-CoV-2 and influenza viruses by targeting the hosts.
• In place of antivirals that directly target the virus in question, the team, co-led by researchers at IISER Mohali and IIT Ropar, attempted the host-directed therapy. Till date, no approved host-directed drugs are available for either SARS-CoV-2 or influenza virus.
• In both cultured cells and animal studies, the small molecules that were synthesised by team at the Department of Chemistry, IIT Ropar showed over 95% efficacy in halting the infection of cells by SARS-CoV-2 and influenza viruses.
• While antivirals that target the virus become ineffective once the virus develops resistance, drugs that target the host cells to prevent the virus from infecting them, are expected to remain effective even when the virus evolves by accumulating mutations.
• There is already evidence that the current FDA-approved drugs for treating SARS-CoV-2 and influenza virus infection are losing their efficacy due to the emergence of drug-resistant virus strains. In host-directed therapy, the challenge is that molecules can very often turn out to be toxic to the host cells, the reason why this approach has not been widely adopted.
• The small molecules were not only effective (over 95%) against both SARS-CoV-2 and influenza viruses, they were not toxic to either cultured cells or mice even after prolonged exposure.
• Of the 28 molecules screened, one molecule—1,3-diphenylurea derivative (DPUD) was able to block both SARS-CoV-2 and influenza virus infection by almost 100% in cells without being toxic to the cells.
• These molecules carry chloride ions into the cell, thereby leading to a large accumulation of chloride inside the cell, disturbing the chloride equilibrium. When the chloride equilibrium is disturbed, some endocytic pathways become non-functional. As a result, the viruses fail to enter the cells and establish infection.
• The small molecules were found to be highly effective when tested against H1N1 and H3N2 influenza virus sub-types and the SARS-CoV-2 Wuhan, Delta, and two Omicron variants of concern.