Targeting heat-shock protein 90 could be a new antiviral approach that is not prone to the development of drug resistance. The 17-amino-17-demethoxygeldanamycin derivatives could be novel agents with potential antiviral activity.
Two novel spirooliganones A (1) and (2), a pair of spiro carbon epimers, with a rare dioxaspiro skeleton were isolated from the roots of Illicium oligandrum. The structures were fully determined by spectroscopic analysis and chemical methods, especially modified Mosher's method, and X-ray diffraction analysis. Spirooliganone B was found to exhibit more potent activities against coxsackie virus B3 and influenza virus A (H3N2) (IC50 3.70-5.05 μM) than spirooliganone A. The biosynthetic pathway involving a hetero-Diels-Alder reaction of the epimers was proposed.
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.
A series of novel N-substituted sophocarpinic acid derivatives was designed, synthesized, and evaluated for their anti-enteroviral activities against coxsackievirus type B3 (CVB3) and coxsackievirus type B6 (CVB6) in Vero cells. Structure-activity relationship analysis revealed that the introduction of a benzenesulfonyl moiety on the 12-nitrogen atom in (E)-β,γ-sophocarpinic acid might significantly enhance anti-CVB3 activity. Among the derivatives, (E)-12-N-(m-cyanobenzenesulfonyl)-β,γ-sophocarpinic acid (11 m), possessing a meta-cyanobenzenesulfonyl group, exhibited potent activity against CVB3 with a selectivity index (SI) of 107. Furthermore, compound 11 m also showed a good oral pharmacokinetic profile, with an AUC value of 7.29 μM h⁻¹ in rats, and good safety through the oral route in mice, with an LD₅₀ value of >1000 mg kg⁻¹; these values suggest a druggable characteristic. Therefore, compound 11 m was selected for further investigation as a promising CVB3 inhibitor. We consider (E)-β,γ-N-(benzenesulfonyl)sophocarpinic acids to be a novel class of anti-CVB3 agents.
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