Effective inhibition of HCoV-OC43 and SARS-CoV-2 by phytochemicals in vitro and in vivo.

Several coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus OC43 (HCoV-OC43) can cause respiratory infections in humans. To address the need for reliable anti-coronavirus therapeutics, we screened 16 active phytochemicals selected from medicinal plants used in traditional applications for respiratory-related illnesses. An initial screen was completed using HCoV-OC43. The phytochemicals lycorine (LYC), capsaicin (CAP), rottlerin (RTL), piperine (PIP) and chebulinic acid (CHU) inhibited HCoV-OC43-induced cytopathic effect and reduced viral titers by up to four logs. LYC, RTL and CHU also suppressed virus replication and cell death following SARS-CoV-2 infection. In vivo, RTL significantly reduced SARS-CoV-2-induced mortality by approximately 40% in human ACE2 expressing K18 mice. Collectively, these studies indicate that RTL and other phytochemicals have therapeutic potential to reduce SARS-CoV-2 and HCoV-43 infections.