Computational approach for binding prediction of SARS-CoV-2 with neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a severe pandemic and caused enormous global health and economical damage. Since December 2019, more than 197 million cases have been reported, causing 4.2 million deaths. In the settings of pandemic it is an urgent necessity for the development of an effective COVID-19 treatment. While in-vitro screening of hundreds of antibodies isolated from convalescent patients is challenging due to its high cost, use of computational methods may provide an attractive solution in selecting the top candidates. Here, we developed a computational approach (SARS-AB) for binding prediction of spike protein SARS-CoV-2 with monoclonal antibodies. We validated our approach using existing structures in the protein data bank (PDB), and demonstrated its prediction power in antibody-spike protein binding prediction. We further tested its performance using antibody sequences from the literature where crystal structure is not available, and observed a high prediction accuracy (AUC = 99.6%). Finally, we demonstrated that SARS-AB can be used to design effective antibodies against novel SARS-CoV-2 mutants that might escape the current antibody protections. We believe that SARS-AB can significantly accelerate the discovery of neutralizing antibodies against SARS-CoV-2 and its mutants.

An antibody that neutralizes SARS-CoV-1 and SARS-CoV-2 by binding to a conserved spike epitope outside the receptor binding motif.

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as the Omicron variants that are highly transmissible and immune evasive, underscores the need to develop therapeutic antibodies with broad neutralizing activities. Here, we used the LIBRA-seq technology, which identified SARS-CoV-2-specific B cells via DNA barcoding and subsequently single-cell sequenced BCRs, to identify an antibody, SW186, which could neutralize major SARS-CoV-2 variants of concern, including Beta, Delta, and Omicron, as well as SARS-CoV-1. The cryo-EM structure of SW186 bound to the receptor binding domain (RBD) of the viral spike protein showed that SW186 interacted with an epitope of the RBD that is not at the interface of its binding to the ACE2 receptor but is highly conserved among SARS coronaviruses. This epitope encompasses a glycosylation site (N343) of the viral spike protein. Administration of SW186 in mice after they were infected with SARS-CoV-2 Alpha, Beta, or Delta variants reduced the viral loads in the lung. These results demonstrated that SW186 neutralizes diverse SARS coronaviruses by binding to a conserved RBD epitope, which could serve as a target for further antibody development.

Experience in Neurosurgery During the Prevalence of COVID-19.

In order to summarize the experience of neurosurgery in The Third People's Hospital of Hubei Province after the outbreak of COVID-19 in 2019, 28 patients were admitted from January 5, 2020 to February 17, 2020. A series of department formulates and constant improvements were made, including elective operation cancellation, altered conventional outpatient service into online outpatient service, strict control of inter department consultation prevention and entering the department, improvements in operation and treatment processes, and strict ward management. As a result, 1 patient with hypertensive cerebral hemorrhage and deep vein thrombosis of the right lower extremity died suddenly due to pulmonary embolism during anticoagulation treatment. Two patients with deep coma gave up treatment and died. No patient was confirmed to be infected with COVID-19 in hospital. One doctor had a low fever and cough in January, and CT showed a small nodule in the lower left lung. After 2 weeks isolation and oral anti-infective drugs, the chest nodule disappeared. One nurse was isolated as a close contact with infected parents. One nurse was confirmed to be infected with COVID-19 in a mild symptom. She was discharged after being cured in the infected department. In conclusion, measures like sufficient theoretical training and protection upgrading for medical staff, continuous improvement on the understanding of COVID-19 characteristics and transmission routes, formulation of strict department management system, monitoring of patients and their families, could effectively deal with the epidemic situation in the neurosurgery department.