Low rotational barriers for the most dynamically active methyl groups in the proposed antiviral drugs for treatment of SARS-CoV-2, apilimod and tetrandrine

A recent screening study highlighted a molecular compound, apilimod, for its efficacy against the SARS-CoV-2 virus, while another compound, tetrandrine, demonstrated a remarkable synergy with the benchmark antiviral drug, remdesivir. Here, we find that because of significantly reduced potential energy barriers, which also give rise to pronounced quantum effects, the rotational dynamics of the most dynamically active methyl groups in apilimod and tetrandrine are much faster than those in remdesivir. Because dynamics of methyl groups are essential for biochemical activity, screening studies based on the computed potential energy profiles may help identify promising candidates within a given class of drugs.

Automated summary

A recent screening study identified apilimod as effective against SARS-CoV-2 virus and tetrandrine showed synergy with remdesivir. The rotational dynamics of methyl groups in apilimod and tetrandrine are faster than in remdesivir due to reduced energy barriers, which may impact their bioactivity. Screening studies based on computed potential energy profiles can help identify promising drug candidates within a drug class.