Novel effective antivirals against SARS-CoV-2 are needed because of the emergence of novel variants and the potential risk of SARS-CoV-2/MERS-CoV recombination. The SARS-CoV-2 main protease (Mpro) is a promising antiviral target. Mpro presents a His41-Cys145 catalytic dyad in the central part of its active site, which confers a natural advantage for developing covalent drugs.

Viral proteases are well-established therapeutic targets in HIV and hepatitis C virus infections. Following the recent COVID-19 pandemic, one of the strategies in place is SARS-CoV-2 main protease (Mpro) inhibition, given the crucial role of SARS-CoV-2 Mpro in the replication of the virus.

Research led by investigators at Ghent University in Belgium showed dysregulation of the complement part of the immune system, regulated by the pro-inflammatory protein interleukin (IL)-6, is a key driver of severe COVID-19 and a good target for drugs to treat the effects of the disease. Writing in the Aug. 23, 2023, issue of Science Translational Medicine, the researchers also described a cellular map of the alterations seen in the complement system during COVID-19 related respiratory deterioration for use in future research.

The COVID-19 pandemic might be officially over, but future variants could still pose a threat, and serious health consequences of the causative virus continue to arise, a fact that has prompted the U.S. government to offer Regeneron Pharmaceuticals Inc. about $326 million to develop and manufacture a next-generation COVID-19 monoclonal antibody therapy.

A study from Weill Cornell Medicine and The Jackson Laboratory has described the epigenetic mark SARS-CoV-2 left on immune system stem cells in the most severe cases of COVID-19 early in the pandemic, before the development of vaccines. In their work published in Cell on Aug. 18, 2023, the researchers presented a new methodology to analyze the epigenetic changes in monocytes and circulating hematopoietic stem and progenitor cells (HSPCs) that give rise to monocytes. That allowed corresponding author Steven Josefowicz and his colleagues to see if there were already changes induced by COVID-19 before HSPCs differentiated into monocytes.

How severe a viral infection is depends on how much the virus is replicating, damaging cells as it does so, and on the response of the immune system. Or so one would think. “Some of the most severe cases of COVID-19 are happening in the absence of replicating virus,” Joseph Guarnieri told BioWorld. In work published in Science Translational Medicine on Aug. 9, 2023, Guarnieri and his colleagues have described how those severe cases unfold, even as there is no replicating virus to be found.