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

被引:0
作者
Kiarie, Irene Wanjiru [1 ,2 ]
Hoffka, Gyula [1 ,2 ]
Laporte, Manon [3 ]
Leyssen, Pieter [3 ,4 ]
Neyts, Johan [3 ,4 ]
Tozser, Jozsef [1 ]
Mahdi, Mohamed [1 ]
机构
[1] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Lab Retroviral Biochem, H-4032 Debrecen, Hungary
[2] Univ Debrecen, Doctoral Sch Mol Cell & Immune Biol, H-4032 Debrecen, Hungary
[3] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol Immunol & Transplantat, Lab Virol & Chemotherapy, B-3000 Leuven, Belgium
[4] European Res Infrastruct Highly Pathogen Agents ER, Rue Trone 98, B-1050 Brussels, Belgium
来源
VIRUSES-BASEL | 2024年 / 16卷 / 10期
关键词
HIV-2; integrase strand transfer inhibitor (INSTIs); HIV; integrase; lenacapavir; SARS-CoV-2; PHENOTYPIC SUSCEPTIBILITY; DRUG-RESISTANCE; VIRUS; DOLUTEGRAVIR; ETRAVIRINE; ACCURACY; PROTEASE; OUTCOMES; DOCKING; BIOLOGY;
D O I
10.3390/v16101607
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:15
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