Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2

Abstract

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a CFDA-approved macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway

“…Repurposing old drugs in treating other diseases is a technique with many advantages including time and cost savings, since the safety and toxicity of candidate drugs have already been clearly studied [17]. Carrimycin is a Chinese Food and Drug Administration (CFDA)-approved macrolide antibiotic [32]. Here, we firstly isolated the active component of carrimycin, ISP-I, and verified its satisfying anti-NSCLC effect both in vitro and in vivo.…”

Carbohydrate-based drugs launched during 2000−2021

“…Thus, carrimycin ( 14 ) was approved by NMPA for pneumonia treatment in 2019. Of note, carrimycin ( 14 ) displays a broad-spectrum antiviral activity against human coronaviruses, including COVID-19, and is preferentially distributed in the lungs by oral administration 161 . As a result, several clinical trials are currently under way to investigate the efficacy of carrimycin ( 14 ) against COVID-19.…”

Research and development of Chinese anti-COVID-19 drugs

“…Previous studies found that carrimycin exerts efficacy after the virus enter cells, which can reduce the newly synthesized RNA level of coronavirus, indicating that carrimycin can play an anti-coronavirus role by affecting coronavirus RNA replication. In addition, Carrimycin can regulate the interferon signaling pathway JAK/stat, ISGS, and PI3K Akt mTOR signaling pathway 15 . A phase Ⅲ clinical trials of carrimycin in hospitalized patients with severe COVID-19 have been completed.…”