HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus.
A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.
Yamamoto
Norio
N
Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. yamamoto.mmb@tmd.ac.jp
Yang
Rongge
R
Yoshinaka
Yoshiyuki
Y
Amari
Shinji
S
Nakano
Tatsuya
T
Cinatl
Jindrich
J
Rabenau
Holger
H
Doerr
Hans Wilhelm
HW
Hunsmann
Gerhard
G
Otaka
Akira
A
Tamamura
Hirokazu
H
Fujii
Nobutaka
N
Yamamoto
Naoki
N
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D007928:Lethal Dose 50; D019888:Nelfinavir / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D013997:Time Factors; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019888:Nelfinavir; D019438:Ritonavir