Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have posed serious threats to humans and animals, which urgently calls for effective broad‐spectrum antivirals. RNA‐dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthes...
Gespeichert in:
Veröffentlicht in: | Advanced science 2022-12, Vol.9 (35), p.e2203499-n/a |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have posed serious threats to humans and animals, which urgently calls for effective broad‐spectrum antivirals. RNA‐dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan‐coronaviral therapeutic target. Herein, based on cryo‐electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS‐CoV‐2 RdRp, thus inhibiting SARS‐CoV‐2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS‐CoV‐2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS‐CoV‐2. Moreover, that the RdRp inhibitor GOS has broad‐spectrum anti‐coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS‐CoV‐2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID‐19 pandemic and other coronavirus outbreaks.
Gossypol is identified as an effective inhibitor against SARS‐CoV‐2 RNA‐dependent RNA polymerases. It exhibits excellent antiviral activity against SARS‐CoV‐2 and its variants of concern as well as all examined viruses from the four main phylogenetic branches of coronaviruses, which makes gossypol a novel broad‐spectrum anti‐coronavirus inhibitor that offers a potential treatment option for current COVID‐19 and future coronavirus infections. |
---|---|
ISSN: | 2198-3844 2198-3844 |
DOI: | 10.1002/advs.202203499 |