A List of Research Progresses on SARS-CoV-2 (Part One)

Posted April 26, 2020 by Bonnibelle

Coronaviruses are a large family of viruses widely found in nature. They are named after the corona-like fibrils on their virions. The new coronavirus is a newly discovered pathogen in humans.

The novel coronavirus

Coronaviruses are a large family of viruses widely found in nature. They are named after the corona-like fibrils on their virions. The new coronavirus is a newly discovered pathogen in humans.

Previously, the coronaviruses known to the medical profession are a group of viruses that can cause respiratory infections in humans and animals. Not only have they caused SARS, but more commonly, they have caused various diseases such as the common cold. The clinical symptoms include acute and severe respiratory diseases, such as fever, cough, shortness of breath, and dyspnea; in addition, most cases have pneumonia, and some cases have rapid renal failure and death.

The classification and evolutionary origin of novel coronavirus

Coronavirus is an important pathogen that can only infect vertebrates, and can cause respiratory and digestive tract and nervous system diseases in humans and animals. Coronavirus belongs to the Coronavirus subfamily in the Coronaviridae family of the Coronaviridae, which includes 4 genera: α-Coronavirus, β-Coronavirus, γ-Coronavirus, δ-Coronavirus. Different coronaviruses show different host range and tissue tropism. Generally, alpha coronavirus and beta coronavirus infect mammals, such as humans and camels. In contrast, γ-Coronavirus and δ-Coronavirus can infect birds and fish, but some of them can also infect mammals, such as δ-Coronavirus can infect pigs. SARS-CoV-2 is the seventh known coronavirus that can infect humans. The remaining six are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKUI, SARS-COV and MERS-CoV. Zhou P Et al. found that the whole genome sequence of SARS-CoV-2 is about 76% homologous to the sequence of SARS-CoV, while the sequence homology to Bat CoV RaTG13 in the Chinese crown bat in Yunnan is up to 96%. Among them, the S gene sequence identity is 93.1%, which is currently known as the most homologous strain. At the same time, genetic and phylogenetic analysis results of seven conserved non-structural proteins show that SARS-CoV-2 belongs to the β-coronavirus genus C lineage.

The latest research progress on novel coronavirus

Science: the susceptibility of cats, dogs and humans
Recently, relying on the National High-level Laboratory for Animal Disease Prevention and Control and the State Key Laboratory of Veterinary Biotechnology, the team of Bu Zhigao, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, the team of Academician Chen Hualan, and the researcher Wu Guizhen and Researcher Tan Wenjie of the Chinese Institute of CDC Viral Disease Prevention and Control, etc., systematically studied the susceptibility of dogs, cats, pigs, chickens, ducks and other common pets, domestic animals, poultry, and model experimental animals ferret, who are in close contact with humans, to SARS-CoV-2. Through experimental infection with SARS-CoV-2, the clinical manifestations and pathological changes of vaccinated animals and cohabiting animals were observed, and the viral load of organs and tissues, the discharge of respiratory and enteroviruses, and the positive of antibodies against SARS-CoV-2 virus in animals were detected. The research results were published online in "Science".

The study found that SARS-CoV-2 has a weak replication ability in dogs, pigs, chickens and ducks, but can efficiently replicate in the upper respiratory tract of ferrets and the respiratory and digestive systems of cats. Experimental infected cats can transmit SARS-CoV-2 to cats through the air; some cats can cause severe morbidity or even death after infection. The incidence of young cats is obviously more serious than that of older cats. Histopathological observations confirmed that virus-infected cats can cause varying degrees of lung inflammation and intestinal mucosal damage; immunohistochemical studies have found epithelial and olfactory bulb cells of the upper respiratory tract (nasal cavity, palate, tonsils), mucosal gland epithelial cells of the trachea and bronchial mucosa, intestinal mucosal epithelium and other parts of the body have a large number of viral infections. The results show that ferrets can be used as animal models for SARS-CoV-2 vaccine and drug evaluation; dogs, pigs, chickens and ducks are not susceptible to SARS-CoV-2, and have important guiding significance for virus host tracing; more importantly, cats are highly susceptible to SARS-CoV-2. The study calls for close monitoring and protection of cats in epidemic areas to avoid contact with the source of infection and prevent them from becoming possible hosts of transmission or storage.

Science: high-resolution structure of the new coronavirus RNA-dependent RNA polymerase (redcivir target)
The outbreak of a new coronavirus has caused a pandemic worldwide, resulting in tens of thousands of infected and dead people worldwide. Mpro (hydrolase) and Rdrp (RNA-dependent RNA polymerase) are considered to be two important targets of the new coronavirus. On January 26, 2020, Rao Zihe and his team shared the atomic coordinates of the Mpro structure (more than 300 domestic and foreign universities, scientific research institutes, and pharmaceutical companies) with the domestic and foreign countries. On February 5, they were publicly obtained from the international PDB database, " structure of month "(that is, the" star structure "of the PDB library in February). Related work was officially published in Nature on April 9 with the title "Structure of Mpro from COVID-19 virus and discovery of its inhibitors".

RNA-dependent RNA polymerase (RdRp, also known as nsp12) catalyzes the synthesis of viral RNA within the virus. It is a core component of coronavirus replication, and it is also the main target of antiviral drugs such as redcivir.

On April 10, 2020, Academician Rao Zi and academician led the New Coronavirus Research Group (main members include Wang Quan of Shanghai University of Science and Technology and Lou Zhiyong of Tsinghua University, both co-corresponding authors of this article) published in Science magazine Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target, reports the cryo-electron microscopy structure of the new full-length coronavirus nsp12 and cofactors nsp7 and nsp8, with a resolution of 2.9 Angstroms (protein structure database PDB ID: 6M71). The high-resolution virus RdRp is an important breakthrough. The related work was previously published on the bioprinter platform bioRxiv on March 17.

Important biomarkers for COVID-19 patients were found
The Proteome Big Data Laboratory led by PI Guo Tiannan of the School of Life Sciences at West Lake University has recently made important discoveries in the research of new coronaviruses. Together with the cooperative team, they systematically detected protein and metabolite molecules in the blood of patients with new coronary pneumonia, and found that there are many unique molecular changes in the serum of severe patients, and found a series of biomarkers, which are expected to provide guidance for the prediction of mild and critical patients. Related research results have been launched on the pre-printed platform medRxiv at 0:15 on April 8, Beijing time.

The molecular details of the complex of Radecivir and the target is obtained
Due to the rapid increase of new cases, Coronavirus Disease (COVID-19) quickly attracted global attention in 2019, and the pathogen was identified as SARS-CoV-2. As of April 10, 2020, there were more than 1.6 million confirmed cases worldwide and more than 96,000 deaths. These figures are updated daily and are expected to increase further. The replication of SARS-CoV-2 requires viral RNA-dependent RNA polymerase (RdRp), which is a direct target of the antiviral drug Remdesivir. Currently, there are no vaccines or drugs available to prevent or treat COVID-19 infection, and most infected patients have received supportive treatment.

On April 9, 2020, Xu Huaqiang, Xu Yechun, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhang Yan from Zhejiang University and Zhang Shuyang from Tsinghua University published a newsletter entitled "Structural Basis for the Inhibition of the RNA" on the preprinted platform bioRxiv online without peer review. -Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir "research paper, which identified the natural form of the SARS-CoV-2 RdRp complex or two frozen EM structures with template primer RNA and the antiviral drug Remdesivir.

The structure of the complex indicates that part of the double-stranded RNA template is inserted into the central channel of RdRp, where Remdesivir is incorporated into the first replicated base pair and terminates the strand extension. This structure provides important insights into the working mechanism of viral RNA replication and provides a reasonable template for the design of drugs against viral infections.

To be continued in Part Two…
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Last Updated April 26, 2020