Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected

Journal Article · Sat Dec 05 00:00:00 EST 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.09.007· OSTI ID:21357570

Akerstroem, Sara ^[1]; Gunalan, Vithiagaran ^[1]; Keng, Choong Tat ^[2]; Tan, Yee-Joo ^[2]; Mirazimi, Ali ^[1]

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1. Centre for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, SE-171 82 Solna (Sweden)
2. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos Bldg, 138673 Singapore (Singapore)

Nitric oxide is an important molecule playing a key role in a broad range of biological process such as neurotransmission, vasodilatation and immune responses. While the anti-microbiological properties of nitric oxide-derived reactive nitrogen intermediates (RNI) such as peroxynitrite, are known, the mechanism of these effects are as yet poorly studied. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) belongs to the family Coronaviridae, was first identified during 2002-2003. Mortality in SARS patients ranges from between 6 to 55%. We have previously shown that nitric oxide inhibits the replication cycle of SARS-CoV in vitro by an unknown mechanism. In this study, we have further investigated the mechanism of the inhibition process of nitric oxide against SARS-CoV. We found that peroxynitrite, an intermediate product of nitric oxide in solution formed by the reaction of NO with superoxide, has no effect on the replication cycle of SARS-CoV, suggesting that the inhibition is either directly effected by NO or a derivative other than peroxynitrite. Most interestingly, we found that NO inhibits the replication of SARS-CoV by two distinct mechanisms. Firstly, NO or its derivatives cause a reduction in the palmitoylation of nascently expressed spike (S) protein which affects the fusion between the S protein and its cognate receptor, angiotensin converting enzyme 2. Secondly, NO or its derivatives cause a reduction in viral RNA production in the early steps of viral replication, and this could possibly be due to an effect on one or both of the cysteine proteases encoded in Orf1a of SARS-CoV.

• OSTI ID: 21357570
• Journal Information: Virology, Vol. 395, Issue 1; Other Information: DOI: 10.1016/j.virol.2009.09.007; PII: S0042-6822(09)00555-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOTENSIN
CYSTEINE
ENZYMES
INHIBITION
NITRIC OXIDE
RECEPTORS
RNA
VIRUSES
AMINO ACIDS
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CHALCOGENIDES
DRUGS
GLOBULINS
MEMBRANE PROTEINS
MICROORGANISMS
NITROGEN COMPOUNDS
NITROGEN OXIDES
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PARASITES
PROTEINS
THIOLS
VASOCONSTRICTORS