PubMed Journals: Antivir Chem Chemother

  Source:		PMID: 17176632
  Download:	https://journals.sagepub.com/doi/pdf/10.1177/095632020601700505

    		Antivir Chem Chemother. 2006;17(5):275-84.
			Evaluation of immunomodulators, interferons
			and known in vitro SARS-coV inhibitors for inhibition
			of SARS-coV replication in BALB/c mice.

			Barnard DL(1), Day CW, Bailey K, Heiner
			M, Montgomery R, Lauridsen L, Chan PK, Sidwell

			Author Information
			(1) Institute for Antiviral Research,
			Utah State University, Logan, UT, USA.

			Compounds approved for therapeutic use and
			in vitro inhibitors of severe acute respiratory syndrome
			coronavirus (SARS-CoV) were evaluated for
			inhibition in the mouse SARS-CoV replication
			model. A hybrid interferon, interferon alpha
			(IFN-alpha) B/D, and a mismatched double-stranded
			(ds) RNA interferon (IFN) inducer, Ampligen
			(poly I:poly C124), were the only compounds
			that potently inhibited virus titres in
			the lungs of infected mice as assessed by
			CPE titration assays. When mice were dosed
			intraperitoneally (i.p.) with IFN-alpha
			B/D once daily for 3 days beginning 4 h
			after virus exposure, SARS-CoV replication
			in the lungs of infected mice was reduced
			by 1 log10 at 10,000 and 32,000 IU; at the
			highest dose of 100,000 IU, virus lung titres
			were below detectable limits. Ampligen used
			i.p. at 10 mg/kg 4 h prior to virus exposure
			also reduced virus lung titres to below
			detectable limits. Nelfinavir,
			beta-D-N4-hydroxycytidine, calpain inhibitor
			VI, 3-deazaneplanocin A and Alferon (human
			leukocyte IFN-alpha-n3) did not significantly
			reduce lung virus titres in mice. Anti-inflammatory
			agents, chloroquine, amodiaquin and pentoxifylline,
			were also inactive in vivo, suggesting that
			although they may be useful in ameliorating
			the hyperinflammatory response induced by
			the virus infection, they will not significantly
			reduce the replication of the virus, the
			inducer of inflammatory response. Thus,
			anti-inflammatory agents may only be useful
			in treating virus lung infections if used
			in combination with agents that inhibit
			virus replication. In summary, the data
			suggest that induction of IFN by mismatched
			dsRNA or actual treatment with exogenous
			IFN-alpha can inhibit SARS-CoV replication
			in the lungs of mice.

			DOI: 10.1177/095632020601700505 PMID: 17176632
			[Indexed for MEDLINE]

     			                         Tweet       Print