Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Abstract

Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics. Methods Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package “outbreaker”. The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test. Results From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based sub-clusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became “pure” in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001). Conclusions SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion. Graphic Abstract

SARS-CoV-2 Whole-Genome Sequencing by Ion S5 Technology—Challenges, Protocol Optimization and Success Rates for Different Strains

“…Initially, a limited number of SARS-CoV-2 genome sequences was sufficient for the construction of commonly used molecular tests-at the time of the publication of the CDC 2019-nCoV RT-PCR Diagnostic Panel, less than 500 full genome sequences were included in public databases [4]. However, to understand the virus's transmission patterns, the need for whole-genome studies arose [5][6][7][8]. Moreover, as time progressed and the number of infected people grew, the virus mutated, as expected, with some strains prevailing within regions, countries, or even continents.…”

Mapping of SARS-CoV-2 Spike Protein Evolution During the First and Second Waves of COVID-19 Infections in India

“…The differential level of infections, pathogenicity and transmission in different states could possibly be due to these state-specific mutations. Functional characterization of many of the presently observed mutations has been illustrated in many studies [ 20 , 21 , 27–32 ]. Most of the RBD mutations strengthen the RBD–ACE2 binding supporting the evolution of the virus to more infectious variants [ 21 , 27 , 29 ].…”

“…Functional characterization of many of the presently observed mutations has been illustrated in many studies [ 20 , 21 , 27–32 ]. Most of the RBD mutations strengthen the RBD–ACE2 binding supporting the evolution of the virus to more infectious variants [ 21 , 27 , 29 ]. Mutations N501Y, D614G and others have been found to be associated with reinfection, partial resistance to vaccines and increased transmissibility.…”

“…Mutations N501Y, D614G and others have been found to be associated with reinfection, partial resistance to vaccines and increased transmissibility. Mutation V367F, N354D and T478K in SARS-CoV-2 in RBD has been associated with enhanced hACE2 binding affinity and increased viral infectivity [ 21 , 27 , 29 ]. Mutations L452R and E484Q found in Indian variants have been shown to disrupt the binding between RBD and many known antibodies leading to vaccine escape [ 21 ].…”

Evaluation of the presence of SARS-CoV-2 in vaginal and anal swabs of women with omicron variants of SARS-CoV-2 infection

“…With the evolution of the virus, the affinity of the virus and host receptor ACE2 gradually improves, resulting in further reduction in the concentration of virus required for infection. Therefore, a stronger spreading ability and weaker pathogenicity should be expected as the evolution direction of SARS-COV-2 ( Cao, 2020 ; Liu et al, 2021 ; Cameroni et al, 2022 ).…”