Sumary of Compounds that inhibit coronavirus entry, replication in human cells identified:
- Scientists in the US have identified some existing compounds that can inhibit two key proteins required by the novel coronavirus to gain entry into human cells and reproduce, an advance that may help develop new effective anti-viral drugs for COVID-19..
- Gaining entry into cells deep within the lungs and hijacking the human host cell’s machinery to churn out copies of itself are two of the earliest steps — both essential for viral infection..
- The new study, published in the journal Science Advances, found that some existing compounds can inhibit both the main protease (Mpro), a key viral protein required for SARS-CoV-2 replication inside human cells, and the lysosomal protease cathepsin L, a human protein important for viral entry into host cells..
- “If we can develop compounds to shut down or significantly reduce both processes — viral entry and viral replication — such dual inhibition may enhance the potency of these compounds in treating the coronavirus infection,”.
- All the candidates chosen to pursue target Mpro to block the replication of SARS-CoV-2 within human cells were grown in the laboratory..
- However, the calpain inhibitors, especially XII, actually worked better than GC-376 at killing SARS-CoV-2 in cell cultures, said lead author Michael Sacco, a doctoral student in Chen’s laboratory..
- “We figured if these calpain inhibitors were less effective at inhibiting the virus’s main protease, they must be doing something else to explain their antiviral activity,”.
- They learned from research done by other groups, including collaborator and study co-principal investigator Jun Wang, from UA, that calpain inhibitors can block other proteases, including cathepsin L, a critical human host protease involved in mediating SARS-CoV-2 entry into cells….