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      A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants

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          Significance

          The rapid spread of the virus causing COVID-19, SARS-CoV-2, raises questions about the possibility of a universally effective vaccine. The virus can mutate in a given individual, and these variants can be propagated across populations and time. To understand this process, we analyze 18,514 SARS-CoV-2 sequences sampled since December 2019. We find that neutral evolution, rather than adaptive selection, can explain the rare mutations seen across SARS-CoV-2 genomes. In the immunogenic Spike protein, the D614G mutation has become consensus, yet there is no evidence of mutations affecting binding to the ACE2 receptor. Our results suggest that, to date, the limited diversity seen in SARS-CoV-2 should not preclude a single vaccine from providing global protection.

          Abstract

          The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages.

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          Most cited references32

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

              Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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                Author and article information

                Journal
                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                pnas
                pnas
                PNAS
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                0027-8424
                1091-6490
                22 September 2020
                31 August 2020
                31 August 2020
                : 117
                : 38
                : 23652-23662
                Affiliations
                [1] aEmerging Infectious Diseases Branch, Walter Reed Army Institute of Research , Silver Spring, MD 20910;
                [2] bUS Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, MD 20910;
                [3] cHenry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, MD 20817;
                [4] dCenter for Infectious Diseases Research, Walter Reed Army Institute of Research , Silver Spring, MD 20910;
                [5] eVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109
                Author notes
                3To whom correspondence may be addressed. Email: kayvon.modjarrad.civ@ 123456mail.mil or mrolland@ 123456hivresearch.org .

                Edited by John M. Coffin, Tufts University, Boston, MA, and approved July 25, 2020 (received for review April 30, 2020)

                Author contributions: B.D., E.L., K.M., and M.R. designed research; B.D., E.L., H.B., and Y.L. performed research; M.G.J., P.T.S., M.F.A., S.V., and N.L.M. contributed new reagents/analytic tools; B.D., E.L., H.B., Y.L., D.B.R., and M.R. analyzed data; and B.D., E.L., K.M., and M.R. wrote the paper.

                1B.D. and E.L. contributed equally to this work.

                2K.M. and M.R. contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-3653-4592
                https://orcid.org/0000-0001-6459-2437
                https://orcid.org/0000-0002-3501-3974
                https://orcid.org/0000-0001-7038-2671
                https://orcid.org/0000-0001-5684-9538
                https://orcid.org/0000-0002-6808-7232
                https://orcid.org/0000-0002-2696-6116
                https://orcid.org/0000-0002-6378-6288
                https://orcid.org/0000-0001-5882-5548
                https://orcid.org/0000-0002-6514-5572
                https://orcid.org/0000-0003-3650-8490
                Article
                202008281
                10.1073/pnas.2008281117
                7519301
                32868447
                0b8f4802-46c7-4460-8dcb-3d19f99ad906
                Copyright © 2020 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                History
                Page count
                Pages: 11
                Categories
                530
                Biological Sciences
                Evolution
                Custom metadata
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                sars-cov-2,evolution,vaccine
                sars-cov-2, evolution, vaccine

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