Malik Y A
University Malaya, Faculty of Medicine, Department of Medical Microbiology, Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Malays J Pathol. 2020 Apr;42(1):3-11.
were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.
自2002年SARS-CoV被发现以来,陆续有冠状病毒被识别出来。随着最近SARS-CoV-2的检测发现,目前已知有七种人类冠状病毒。引起轻症的是229E、OC43、NL63和HKU1,致病的种类是SARS-CoV、MERS-CoV和SARS-CoV-2。冠状病毒(目为网巢病毒目,科为冠状病毒科,亚科为正冠状病毒亚科)呈球形(直径125nm),表面有包膜,包膜上有棒状刺突,形似日冕。在螺旋对称的核衣壳内是大型正链单链RNA。在四个冠状病毒属(α、β、γ、δ)中,人类冠状病毒(HCoVs)被归类为α冠状病毒属(HCoV-229E和NL63)和β冠状病毒属(MERS-CoV、SARS-CoV、HCoV OC43和HCoV-HKU1)。SARS-CoV-2是一种β冠状病毒,与两种源自蝙蝠的类冠状病毒bat-SL-CoVZC45和bat-SL-CoVZXC21有相当密切的亲缘关系。即便如此,其基因组与典型冠状病毒的基因组相似。SARS-CoV和MERS-CoV起源于蝙蝠,SARS-CoV-2似乎也是如此。果子狸作为SARS-CoV的中间宿主,单峰骆驼作为MERS-CoV的中间宿主,已经证明了中间宿主促进病毒在人类中出现的可能性。人传人主要通过呼吸道飞沫的密切接触、与感染者的直接接触或与受污染物体及表面的接触来实现。冠状病毒基因组包含四种主要结构蛋白:刺突(S)、膜(M)、包膜(E)和核衣壳(N)蛋白,所有这些蛋白都在基因组的3'端编码。S蛋白介导病毒与宿主细胞表面受体的结合导致融合及随后的病毒进入。M蛋白是最丰富的蛋白,决定了病毒包膜的形状。E蛋白是主要结构蛋白中最小的,参与病毒组装和出芽。N蛋白是唯一与RNA基因组结合的蛋白,也参与病毒组装和出芽。冠状病毒的复制始于附着和进入。病毒与宿主细胞的附着由S蛋白与其特定受体之间的相互作用启动。受体结合后,病毒通过蛋白酶对S蛋白的切割进入宿主细胞胞质溶胶,随后病毒膜与细胞膜融合。下一步是从病毒粒子基因组RNA翻译复制酶基因,然后翻译和组装病毒复制酶复合物。复制和亚基因组RNA合成后,进行衣壳化,形成成熟病毒。组装后,病毒粒子通过囊泡运输到细胞表面并通过胞吐作用释放。