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GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.

ABSTRACT: The HIV-1 capsid is the target for the antiviral drugs GS-CA1 and Lenacapavir (GS-6207). We investigated the mechanism by which GS-CA1 and GS-6207 inhibit HIV-1 infection. HIV-1 inhibition by GS-CA1 did not require CPSF6 in CD4⁺ T cells. Contrary to PF74 that accelerates uncoating of HIV-1, GS-CA1 and GS-6207 stabilized the core. GS-CA1, unlike PF74, allowed the core to enter the nucleus, which agrees with the fact that GS-CA1 inhibits infection after reverse transcription. Unlike PF74, GS-CA1 did not disaggregate preformed CPSF6 complexes in nuclear speckles, suggesting that PF74 and GS-CA1 have different mechanisms of action. GS-CA1 stabilized the HIV-1 core, possibly by inducing a conformational shift in the core; in agreement, HIV-1 cores bearing N74D regained their ability to bind CPSF6 in the presence of GS-CA1. We showed that GS-CA1 binds to the HIV-1 core, changes its conformation, stabilizes the core, and thereby prevents viral uncoating and infection.

SUBMITTER: Selyutina A

PROVIDER: S-EPMC8718827 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.

Selyutina Anastasia A Hu Pan P Miller Sorin S Simons Lacy M LM Yu Hyun Jae HJ Hultquist Judd F JF Lee KyeongEun K KewalRamani Vineet N VN Diaz-Griffero Felipe F

iScience 20211209 1

The HIV-1 capsid is the target for the antiviral drugs GS-CA1 and Lenacapavir (GS-6207). We investigated the mechanism by which GS-CA1 and GS-6207 inhibit HIV-1 infection. HIV-1 inhibition by GS-CA1 did not require CPSF6 in CD4<sup>+</sup> T cells. Contrary to PF74 that accelerates uncoating of HIV-1, GS-CA1 and GS-6207 stabilized the core. GS-CA1, unlike PF74, allowed the core to enter the nucleus, which agrees with the fact that GS-CA1 inhibits infection after reverse transcription. Unlike PF7 ...[more]

PMID: 35005542

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Dataset Information

GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.

Publications

GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.

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