title: HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus.
abstract: 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.
authors.affiliation: 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
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Rongge
authors.initials: R
authors.lastname: Yang
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yoshinaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Amari
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakano
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Holger
authors.initials: H
authors.lastname: Rabenau
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hunsmann
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: 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*
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019888:Nelfinavir; D019438:Ritonavir