Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected.
Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected.
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DOI：
10.1016/j.virol.2009.09.007
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发表时间：
2009-12-05
期刊：
影响因子：
3.7
通讯作者：
Mirazimi A
中科院分区：
文献类型：
--
作者：
Akerström S;Gunalan V;Keng CT;Tan YJ;Mirazimi A
一氧化氮是一种重要的分子，在神经传递、血管扩张和免疫反应等广泛的生物学过程中发挥着关键作用。尽管一氧化氮衍生的活性氮中间体(RNI)如过氧亚硝酸盐的抗微生物特性已为人所知，但这些作用的机理尚不清楚。严重急性呼吸综合征冠状病毒(SARS-CoV)属于冠状病毒科，于2002-2003年首次发现。SARS患者的死亡率从6%到55%不等。我们先前已经证明，一氧化氮在体外通过一种未知的机制抑制SARS-CoV的复制周期。在本研究中，我们进一步探讨了一氧化氮对SARS冠状病毒抑制过程的机制。我们发现，NO与超氧化物反应生成的NO在溶液中的中间产物过氧亚硝酸盐对SARS冠状病毒的复制周期没有影响，这表明这种抑制作用要么直接受到NO的影响，要么是过氧亚硝酸盐以外的其他衍生物的作用。最有趣的是，我们发现NO通过两种不同的机制抑制SARS-CoV的复制。首先，NO及其衍生物导致新生表达的刺突蛋白(S)的棕榈酰化水平降低，从而影响S蛋白与其同源受体血管紧张素转换酶2之间的融合。其次，在病毒复制的早期，NO及其衍生物导致病毒核糖核酸产量减少，这可能是由于对SARS冠状病毒Orf1a中编码的两种半胱氨酸蛋白酶之一或两种酶的影响。
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.
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影响因子：
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