TY - JOUR

T1 - Structure-Based Design, Synthesis, and Biological Evaluation of the Cage-Amide Derived Orthopox Virus Replication Inhibitors

AU - Mozhaitsev, Evgenii S

AU - Suslov, Evgeniy V

AU - Rastrepaeva, Daria A

AU - Yarovaya, Olga I

AU - Borisevich, Sophia S

AU - Khamitov, Edward M

AU - Kolybalov, Dmitry S

AU - Arkhipov, Sergey G

AU - Bormotov, Nikolai I

AU - Shishkina, Larisa N

AU - Serova, Olga A

AU - Brunilin, Roman V

AU - Vernigora, Andrey A

AU - Nawrozkij, Maxim B

AU - Agafonov, Alexander P

AU - Maksyutov, Rinat A

AU - Volcho, Konstantin P

AU - Salakhutdinov, Nariman F

N1 - Acknowledgments: Authors would like to acknowledge the Multi-Access Chemical Research Center SB RAS for spectral and analytical measurements. Single-crystal X-ray diffraction data were collected with the equipment of the XRD Facility of the Laboratory of Molecular Design and Ecologically Safe Technologies (MDEST) of the Scientific Educational Center “Institute of Chemical Technology”, Novosibirsk State University.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60.

AB - Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60.

KW - Mice

KW - Animals

KW - Orthopoxvirus

KW - Amides/pharmacology

KW - Variola virus

KW - Vaccinia virus

KW - Communicable Diseases

KW - Virus Replication

UR - https://www.mendeley.com/catalogue/e917f5ed-0a22-30ac-9039-c3f07182bd16/

U2 - 10.3390/v15010029

DO - 10.3390/v15010029

M3 - Article

C2 - 36680072

VL - 15

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 1

M1 - 29

ER -