Pathology

Enzyme

Virus

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Viral replication

Virology

Chemistry

Protease

Ebselen

Papain

Coronavirus

Glutathione peroxidase

Glutathione

Computational biology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Biochemistry

Medicine

Scientific Reports

An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PL pro ) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PL pro . We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PL pro CoV2. Furthermore, we identified, for the first time, inhibitors of PL pro CoV2 showing potency in the nanomolar range. Moreover, we found a difference between PL pro from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.

Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2