Efficacy of Integrase Strand Transfer Inhibitors and the Capsid Inhibitor Lenacapavir against HIV-2, and Exploring the Effect of Raltegravir on the Activity of SARS-CoV-2
Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life cycle, including nuclear importation in the case of lentiviruses and integration targeting events; hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by a few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase. We further evaluated the efficacy of raltegravir and other INSTIs against different variants of SARS-CoV-2; however, contrary to previous in silico findings, the inhibitors did not demonstrate significant antiviral activity.
机构:
Univ Washington, CERID, Seattle, WA 98195 USA
Univ Washington, Dept Med Allergy & Infect Dis, Seattle, WA 98195 USAUniv Washington, CERID, Seattle, WA 98195 USA
Raugi, Dana N.
Pan, Charlotte
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Univ Washington, CERID, Seattle, WA 98195 USA
Univ Washington, Dept Med Allergy & Infect Dis, Seattle, WA 98195 USAUniv Washington, CERID, Seattle, WA 98195 USA
Pan, Charlotte
Sow, Papa Salif
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CHNU Fann, Serv Malad Infect, Dakar, SenegalUniv Washington, CERID, Seattle, WA 98195 USA
Sow, Papa Salif
Seydi, Moussa
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CHNU Fann, Serv Malad Infect, Dakar, SenegalUniv Washington, CERID, Seattle, WA 98195 USA
Seydi, Moussa
Mullins, James I.
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Univ Washington, Dept Microbiol, Lab Med, Seattle, WA 98195 USA
Univ Washington, Dept Med, Lab Med, Seattle, WA 98195 USAUniv Washington, CERID, Seattle, WA 98195 USA
机构:Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Ma, Ling
Li, Quanjie
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Li, Quanjie
Xie, Yongli
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Xie, Yongli
Zhao, Jianyuan
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Zhao, Jianyuan
Yi, Dongrong
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Yi, Dongrong
Guo, Saisai
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Guo, Saisai
Guo, Fei
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Chinese Acad Med Sci, Inst Pathogen Biol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Guo, Fei
Wang, Jing
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Wang, Jing
Yang, Long
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Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin 301617, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China
Yang, Long
Cen, Shan
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Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China