Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Yu, Danwei; Zhu, Yuanmei; Yan, Hongxia; Wu, Tong; Chong, Huihui; He, Yuxian
• Is Part Of: Emerging microbes & infections. Volume 10:Issue 1(2021)
• Page Start: 810
• Page End: 821
• Publication Date: 2021-01-01
• Subjects: Coronavirus -- SARS-CoV-2 -- HIV-1 -- fusion inhibitor -- lipopeptide; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2021.1917309
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: EK1 peptide is a membrane fusion inhibitor with broad-spectrum activity against human coronaviruses (CoVs). In the outbreak of COVID-19, we generated a lipopeptide EK1V1 by modifying EK1 with cholesterol, which exhibited significantly improved antiviral activity. In this study, we surprisingly found that EK1V1 also displayed potent cross-inhibitory activities against divergent HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates. Consistently, the recently reported EK1 derivative EK1C4 and SARS-CoV-2 derived fusion inhibitor lipopeptides (IPB02 ∼ IPB09) also inhibited HIV-1 Env-mediated cell–cell fusion and infection efficiently. In the inhibition of a panel of HIV-1 mutants resistant to HIV-1 fusion inhibitors, EK1V1 and IPB02-based inhibitors exhibited significantly decreased or increased activities, suggesting the heptad repeat-1 region (HR1) of HIV-1 gp41 being their target. Furthermore, the sequence alignment and molecular docking analyses verified the target site and revealed the mechanism underlying the resistance. Combined, we conclude that this serendipitous discovery provides a proof-of-concept for a common mechanism of viral fusion and critical information for the development of broad-spectrum antivirals.