Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins

Takuya Kobayakawa; Masaru Yokoyama; Kohei Tsuji; Masayuki Fujino; Masaki Kurakami; Sayaka Boku; Miyuki Nakayama; Moemi Kaneko; Nami Ohashi; Osamu Kotani; Tsutomu Murakami; Hironori Sato; Hirokazu Tamamura

doi:10.3390/biom11020208

Biomolecules (Feb 2021)

Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins

Takuya Kobayakawa,
Masaru Yokoyama,
Kohei Tsuji,
Masayuki Fujino,
Masaki Kurakami,
Sayaka Boku,
Miyuki Nakayama,
Moemi Kaneko,
Nami Ohashi,
Osamu Kotani,
Tsutomu Murakami,
Hironori Sato,
Hirokazu Tamamura

Affiliations

Takuya Kobayakawa: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Masaru Yokoyama: Pathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan
Kohei Tsuji: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Masayuki Fujino: AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
Masaki Kurakami: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Sayaka Boku: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Miyuki Nakayama: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Moemi Kaneko: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Nami Ohashi: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan
Osamu Kotani: Pathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan
Tsutomu Murakami: AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
Hironori Sato: Pathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan
Hirokazu Tamamura: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan

DOI: https://doi.org/10.3390/biom11020208
Journal volume & issue: Vol. 11, no. 2
p. 208

Abstract

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The capsid of human immunodeficiency virus type 1 (HIV-1) is a shell that encloses viral RNA and is highly conserved among many strains of the virus. It forms a conical structure by assembling oligomers of capsid (CA) proteins. CA dysfunction is expected to be an important target of suppression of HIV-1 replication, and it is important to understand a new mechanism that could lead to the CA dysfunction. A drug targeting CA however, has not been developed to date. Hydrophobic interactions between two CA molecules via Trp184/Met185 in CA were recently reported to be important for stabilization of the multimeric structure of CA. In the present study, a small molecule designed by in silico screening as a dipeptide mimic of Trp184 and Met185 in the interaction site, was synthesized and its significant anti-HIV-1 activity was confirmed. Structure activity relationship (SAR) studies of its derivatives were performed and provided results that are expected to be useful in the future design and development of novel anti-HIV agents targeting CA.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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