SARS-CoV-2 Reinfection by Omicron Variant in Shaanxi Province, China, December 2022 to February 2023 (preprint)

Background Before December 2022, we had not reported a patient in Shaanxi province, China, who had been reinfected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since then, China has refined its strategy for response to coronaviruses. The purpose of this study was to determine the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections and compare the severity of the first and second episodes of infection in Shaanxi Province, China.Methods We used the epidemiological survey system with the electronic questionnaires to investigated the possibility of SARS-CoV-2 reinfection among those who previously were infected with coronavirus disease 2019 during the Omicron predominant infection wave beginning in December 2022. Logistic regression model was used to test the influencing factors of SARS-CoV-2 reinfections.Results The rate of reinfection for Omicron variants was 5.92%, 1.96%, and 1.28% 7–9 months, 4–5 months, and 2–3 months after the primary infection, respectively. The rate of reinfection for Delta variations was 25.10% 11–12 months after the primary infection. There were no significant changes in the severity of infection between first infection and reinfection. Adults between the ages of 18 and 38 and being a medical worker have been associated to an increased chance of reinfection.Conclusions SARS-CoV-2 reinfections might increase over time throughout Omicron variant-dominant infection waves. Large-scale infections are less likely to prevail in the following Omicron epidemic period. It is essential to continuously monitor infection cases as well as emerging SARS-CoV-2 variants.

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors (preprint)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using 'MERS-CoV-2' with both high fatality and transmission rate.

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors (preprint)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

Structural and functional characterizations of altered infectivity and immune evasion of SARS-CoV-2 Omicron variant (preprint)

The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron (preprint)

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summary A sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

Cell-Free Synthetic Biosensors Based on CRISPR/Cas Mediated Cascade Signal Amplification for Precise RNA Detection (preprint)

Synthetic biology has been harnessed to create new diagnostic technologies. However, most synthetic biosensors involve error-prone amplification steps and limitations of accuracy in RNA detection. Here, we report a cell-free synthetic biosensing platform, termed as SHARK ( S ynthetic Enzyme S h ift RNA Signal A mplifier R elated Cas13a K nockdown Reaction), to efficiently and accurately amplify RNA signal by leveraging the collateral cleavage of activated Cas13a to regulate cell-free enzyme synthesis. Based on cascade amplification and customized enzyme output, SHARK behaves a broad compatibility in different scenarios. Using a personal glucose meter, we detected 50 copies/μl SARS-CoV-2 on a SHARK-loaded paper. In addition, when combined with machine learning, SHARK can perform bio-computations and thus provide miRNA patterns for cancer diagnosis and staging. SHARK shows characteristics of precise recognition, cascade amplification and customizable signal outputting in one pot comparisons with established assays based on 64 clinical samples, presenting great potential in developing next-generation RNA detection technology.

Nanometer resolution in situ structure of SARS-CoV-2 post-fusion spike (preprint)

The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of viral genome into host cell. To understand its detailed entry mechanism and develop specific entry inhibitor, the in situ structural information of SARS-CoV-2 spikes in different states are urgently important. Here, by using the cryo-electron microscopic tomograms, we observed spikes of inactivated SARS-CoV-2 virions in both pre-fusion and post-fusion states and solved the nanometer resolution structure of in situ post-fusion spike. With a more complete model compared to previous reports, the relative spatial position between fusion peptide and transmembrane domain was discovered. Novel oligomerizations of spikes on viral membrane were observed, likely suggesting a new mechanism of fusion pore formation.

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2 (preprint)

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

Evolutionary analysis of SARS-CoV-2 spike protein for its different clades (preprint)

Objective: The spike protein of SARS-CoV-2 has become the main target for antiviral and vaccine development. Despite its relevance, there is scarce information about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches. Methods: Two thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region. Results: The haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 x 10-3 nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after eight months of pandemic was similar for each clade. Conclusions: In conclusion, the present evolutionary analysis is relevant since the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail since re-infection by different phylogenetic clades has been reported.

3D8, a nucleic acid-hydrolyzing scFv, confers antiviral activity against SARS-CoV-2 and multiple coronaviruses in vitro (preprint)

The current pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a critical public health threat worldwide. Coronaviruses (subfamily Orthocoronavirinae, family Coronaviridae, order Nidovirales) are a group of enveloped positive-sense single-stranded RNA viruses. Six pathogenic human coronaviruses, likely zoonotic viruses, cause the common cold in humans. A new emerging coronavirus, SARS-CoV-2, become a crucial etiology for the Coronavirus-induced disease 19 (COVID-19). However, effective therapeutics and vaccines against multiple coronaviruses remain unavailable. This study aimed to investigate an antiviral molecule, single chain variable fragment (scFv), against SARS-CoV-2 and other coronaviruses. 3D8, a recombinant scFv, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. Here, we report that 3D8 scFv inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the absence of coronavirus nucleoproteins and infectious particles in 3D8 scFv-treated cells, respectively. In addition, we observed the antiviral effects of 3D8 against HCoV-OC43 and PEDV. In conclusion, this study provides insights into the broad-spectrum antiviral agent of 3D8 scFv; thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 (preprint)

The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was ~100 PFU in aged, male BALB/c mice. Deep sequencing identified three amino acid mutations, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, which significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of mACE2 in complex with the RBD of MASCp36 at 3.7-angstrom resolution elucidates molecular basis for the receptor-binding switch driven by amino acid substitutions. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in mice.

A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2 (preprint)

Mutations and transient conformational movements of receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable, present immune escape routes to SARS-CoV-2. To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, combination of RBD-targeting NAbs and NTD-binding NAb, FC05, dramatically enhanced the neutralization potency in cell-based assays and animal model. Results of competitive SPR assays and cryo-EM structures of Fabs bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in NTD and RBD of S, when immunized in rabbits elicited potent protective immune responses against SARS-CoV-2. These results provide a proof-of-concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response (preprint)

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.

Functional and druggability analysis of the SARS-CoV-2 proteome (preprint)

The infectious coronavirus disease (COVID-19) pandemic, caused by the coronavirus SARS-CoV-2, appeared in December 2019 in Wuhan, China, and has spread worldwide. As of today, more than 22 million people have been infected, with almost 800,000 fatalities. With the purpose of contributing to the development of effective therapeutics, this work provides an overview of the viral machinery and functional role of each SARS-CoV-2 protein, and a thorough analysis of the structure and druggability assessment of the viral proteome. All structural, non-structural, and accessory proteins of SARS-CoV-2 have been studied, and whenever experimental structural data of SARS-CoV-2 proteins were not available, homology models were built based on solved SARS-CoV structures. Several potential allosteric or protein-protein interaction druggable sites on different viral targets were identified, knowledge that could be used to expand current drug discovery endeavors beyond the cysteine proteases and the polymerase complex. It is our hope that this study will support the efforts of the scientific community both in understanding the molecular determinants of this disease and in widening the repertoire of viral targets in the quest for repurposed or novel drugs against COVID-19.

A Novel Approach to Calculate the Case Fatality Rate of COVID-19 in European countries (preprint)

As a result of the global epidemic of coronavirus disease 2019 (COVID-19), many European countries and regions have been strongly affected. The case fatality rate (CFR) is the most important index to evaluate the hazards associated with an epidemic situation. We aimed to present a method to calculate the instant CFR and to evaluate and compare the instant CFR of COVID-19 in the four European countries that have been most impacted: Italy, Spain, France and Germany. The daily COVID-19 case data from January 30, 2020, to July 9, 2020 in Italy, Spain, France and Germany were collected from WHO reports. Death time was calculated as the difference between the peak dates of the number of daily confirmed cases and the number of deaths in each of the four countries. The estimated dates of diagnosis of the declared deaths were a death time prior to the dates of death. The instant fatality rate of COVID-19 was calculated as the ratio of the number of cumulative deaths to the number of cumulative confirmed cases; these deaths and confirmed cases occurred on the same estimated dates of diagnosis. As of July 9, 2020, the COVID-19 death time was 6, 4, 6 and 12 days in Italy, Spain, France and Germany, respectively. The instant CFR of COVID-19 was 14.4%~27.6%, 2.2%~14.7%, 8.2%~25.0% and 2.0%~10.5% in Italy, Spain, France and Germany, respectively. The average CFR of COVID-19 was highest in France (16.7%) and lowest in Germany (5.0%). Since late April 2020, the CFR has stabilized at approximately 15%, 20% and 5% in Italy, France and Germany, respectively. Since early June, 2020, the CFR in Spain has stabilized at approximately 11%. We have established a more accurate way to calculate the CFR that may provide a basis for the prevention and control of infectious diseases.

A new method to calculate the instant case fatality rate of COVID-19 in Wuhan and Hubei of China (preprint)

The worst-hit area of coronavirus disease 2019 (COVID-19) in China was Wuhan City and its affiliated Hubei Province, where the outbreak has been well controlled. The case fatality rate (CFR) is the most direct indicator to evaluate the hazards of an infectious disease. However, most reported CFR on COVID-19 represent a large deviation from reality. We aimed to establish a more accurate way to estimate the CFR of COVID-19 in Wuhan and Hubei and compare it to the reality. The daily case notification data of COVID-19 from December 8, 2019, to May 1, 2020, in Wuhan and Hubei were collected from the bulletin of the Chinese authorities. The instant CFR of COVID-19 was calculated from the numbers of deaths and the number of cured cases, the two numbers occurred on the same estimated diagnosis dates. The instant CFR of COVID-19 was 1.3%-9.4% in Wuhan and 1.2%-7.4% in Hubei from January 1 to May 1, 2020. It has stabilized at 7.69% in Wuhan and 6.62% in Hubei since early April. The cure rate was between 90.1% and 98.8% and finally stabilized at 92.3% in Wuhan and stabilized at 93.5% in Hubei. The mortality rates were 34.5/100 000 in Wuhan and 7.61/100 000 in Hubei. In conclusion, this approach reveals a way to accurately calculate the CFR, which may provide a basis for the prevention and control of infectious diseases.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody (preprint)

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data (preprint)

Background The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Results From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%19.5% and the instant cured rate was 80.0%96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%16.6% and the instant cured rate was 83.4%96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively. Conclusions The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.

SIR model for novel coronavirus-infected transmission process and its application (preprint)

Background: To establish a novel coronavirus-infection transmission process model in Wuhan, and to provide a decision support for epidemic prediction and prevention. Methods: SIR model for novel coronavirus-infection transmission process was built based on the data of the infected persons, discharged patients and discharged patients during the period of isolation and control in Wuhan. Least squares estimation method was used to estimate the key parameters of the model. Results: The changing trend of the predicted value of SIR model was basically consistent with the actual value, and fitting effect was well. Based on the prediction results of model, future development trend of the epidemic showed that the inflection point of the epidemic was the 38th day, namely at the end of February, the peak number of infected persons was about 22000 (excluding clinical diagnosis cases); Different infection intensity and removal intensity had an impact on the development of the epidemic. Conclusion: The SIR model for novel coronavirus-infection transmission process in Wuhan has high veracity. Through the prediction and application of the model, it can provide guidance and advice for the actual epidemic prevention and control, and take effective measures to control the epidemic situation in time.