Pan-coronavirus fusion inhibitors to combat COVID-19 and other emerging coronavirus infectious diseases.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative agent of the currently ongoing coronavirus disease 2019 (COVID‐19) pandemic, has posed a serious threat to global public health. Recently, several SARS‐CoV‐2 variants of concern (VOCs) have emerged and caused numerous cases of reinfection in convalescent COVID‐19 patients, as well as breakthrough infections in vaccinated individuals. This calls for the development of broad‐spectrum antiviral drugs to combat SARS‐CoV‐2 and its VOCs. Pan‐coronavirus fusion inhibitors, targeting the conserved heptad repeat 1 (HR1) in spike protein S2 subunit, can broadly and potently inhibit infection of SARS‐CoV‐2 and its variants, as well as other human coronaviruses. In this review, we summarized the most recent development of pan‐coronavirus fusion inhibitors, such as EK1, EK1C4, and EKL1C, and highlighted their potential application in combating current COVID‐19 infection and reinfection, as well as future emerging coronavirus infectious diseases.