When did SARS-CoV-2 overflow to humans? How does the vaccine deal with mutation? Discussion on articles published by Shi Zhengli and others

 Reporter : He Liping / Publisher : The Paper / http://news.sciencenet.cn/htmlnews/2021/1/451868.shtm / Translation, editing : Gan Yung Chyan, KUCINTA SETIA

Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Novel Coronavirus Pneumonia (COVID-19, covid, CCP pneumonia) all broke out in the past two decades and are caused by different coronavirus strains (CoV). These viruses are believed to originate from bats and then spread to humans through intermediate hosts. SARS-CoV is derived from civet cats in the wild animal market, and MERS-CoV is derived from dromedary camels, but we have not yet determined the direct source of the coronavirus SARS-CoV-2 (covi, CCP virus). Recently, Shi Zhengli and Zhou Peng, researchers at the Wuhan Institute of Virology, Chinese Academy of Sciences, published an article on the spread of the novel coronavirus in the top academic journal Science, entitled "SARS-CoV-2 spillover events". The direct host traceability and the impact of virus mutation were reviewed and discussed. The two authors mentioned mink first. Previously, on 10 November 2020, "Science" published online a study jointly completed by researchers from the Rasmus Medical Center in Rotterdam, the Netherlands. The virologist Bas B. Oude Munnink and others gave an in-depth report on the Netherlands. The 16 minks and the workers working and living there have been infected with covi. Among the 97 farmers, workers and their close contacts, 66 have been infected with covi. The strains of some patients have animal sequence characteristics. This provides evidence for the spread of the CCP virus between animals and people in the mink farms. In addition to mink, a variety of wild or domestic animals may also carry the new coronavirus or related viruses. The article mentioned that some previous experimental virus infection tests and affinity tests of viral spike proteins and receptors have confirmed that the new coronavirus has a wide host range. After the outbreak of the novel coronavirus, some research groups found SARS-related coronaviruses in Chinese horseshoe bats and pangolins smuggled from South Asia. However, the genome sequence comparison results showed that no direct ancestor of covi has been found. Domestic cats, domestic dogs, and park tigers have also been found to be infected by patients with CCP virus, but there is also no evidence that they can infect humans. Shi Zhengli and others believe that they are unlikely to be the source of covi. So far, the World Organization for Animal Health has reported covi infections in mink farms in 8 countries (the Netherlands, Denmark, Spain, France, Sweden, Italy, the United States and Greece). In addition to the spread of farm animals to people, the frozen food supply chain has also attracted great attention. The article mentioned that several small-scale covid outbreaks in many cities in China were caused by seafood or pork contaminated by the virus overseas. There is evidence that covi can survive on the surface of meat and frozen food packaging for 3 weeks and is still contagious. Therefore, the meat of animals infected with covi or food packaging contaminated by the virus may be a source of human infection. This has aroused public attention to public health and agriculture in the prevention and control of covi. Most animals infected with the CCP virus have no obvious clinical manifestations and cannot be judged without routine diagnosis. The authors mentioned that large-scale culling of mink in farms is an effective way to prevent the further spread of the virus, but this does not apply to all domestic animals (if other species are found to be the host of the new coronavirus). Therefore, out of prudent consideration, strict isolation measures should be implemented in poultry farms with high-density populations. The authors also suggest that since the virus can spread between certain animals (such as mink) and humans, similar control strategies should also be implemented in important occupational groups, such as animal breeders, zookeepers, or slaughterhouse workers. However, evidence of the spread of covi between animals and humans other than mink is still relatively limited. The scientific community should conduct research on whether other domestic animals can carry the new coronavirus, whether it can be transmitted to humans, and other related factors of virus spillage. In response to the problem of virus mutation, the authors wrote that it is now widely believed that coronaviruses tend to evolve rapidly when they jump to different species. In order to maintain a low replication error rate, coronaviruses encode several RNA processing and proofreading enzymes, which are thought to improve the fidelity of virus replication. However, viruses tend to reduce this fidelity when adapting to new host species, and the mechanism behind this phenomenon is unclear. Coronavirus spike protein is more prone to mutation, because it is the primary key protein for the virus to infect the host, so it faces the strongest selection pressure. Scientists have observed this molecular evolution in the SARS-CoV genome. The early stage of disease transmission (civet cat to human) is more pressured to adapt than in the later stage (between humans). The authors pointed out that the mutated novel coronavirus in animals may increase its pathology and transmission in the population. Five variants of the new coronavirus have been found in mink. Among them, in Denmark, Cluster 5 is less immunogenic than human new coronavirus in the serum of patients with new coronary pneumonia. This is because the mutation of this variant is located in the spike protein. The Cluster 5 strain infects at least 12 people, but the patient's clinical manifestations, severity, and transmission between infected people are similar to other new coronavirus strains circulating in humans. They emphasized that at present, there is no evidence that any mutation of the mink new crown virus strain can escape the neutralizing effect of antibodies against the human epidemic strain. However, considering the possible spillover risk of covi between humans and certain animals, it is necessary to closely monitor viral genome mutations from infected animals and humans, especially those that affect the development of diagnostic tests, antiviral drugs and vaccines. The vaccine will help control covi but if the virus continues to spill from animals, vaccines against currently circulating strains may face challenges. In the process of spreading between animal and human species, the virus genome is likely to have mutations, which raises concerns. Can current vaccines prevent new strains in the future? The authors mentioned that extensive sequencing of animal and human viral genomes and global data sharing will be the core work of monitoring the impact of key mutations in the viral genome on vaccine efficacy. Laboratory research should detect whether the emergent mutations affect the main characteristics of the virus, including pathogenesis, immunogenicity, and cross-neutralization. In addition, preparations should be made for the development of new variant virus vaccines. In the long run, the relevant authorities should also consider vaccinating animals to avoid agricultural economic losses. Shi Zhengli and others also discussed the source of covi. The genome sequence of the coronavirus carried by bats or pangolins is 90-96% similar to the human novel coronavirus, but whether they are the animal source of the outbreak remains controversial. Genome evolution analysis of bats and pangolin viruses shows that before the covid pandemic, the virus has undergone further adaptation in animal hosts or humans. Therefore, animals with a high population density through natural selection and a suitable novel coronavirus receptor ACE2 may become the direct ancestral host of the new coronavirus. Another argument is about the source of CCP virus. In view of the detection of the novel coronavirus on the surface of some imported food packaging, contact with contaminated, uncooked food may be an important way for the spread of the new coronavirus. In addition, recent studies have detected antibodies to the new coronavirus in serum samples collected from overseas personnel before the covid outbreak, which indicates that covi has existed for some time before the outbreak was discovered. Shi Zhengli and others suggested that before the outbreak, samples from mink, other susceptible animals and people should be retrospectively investigated to identify the host of the virus's ancestors and determine when the virus spilled into humans.