{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:44:16Z","timestamp":1760233456371,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011680","name":"King Fahad Medical City","doi-asserted-by":"publisher","award":["20-66"],"award-info":[{"award-number":["20-66"]}],"id":[{"id":"10.13039\/501100011680","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019\u20132020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.<\/jats:p>","DOI":"10.3390\/v13010136","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:36:05Z","timestamp":1611196565000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural Mapping of Mutations in Spike, RdRp and Orf3a Genes of SARS-CoV-2 in Influenza Like Illness (ILI) Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-2655","authenticated-orcid":false,"given":"Bandar","family":"Alosaimi","sequence":"first","affiliation":[{"name":"Department of Research labs, Research Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia"},{"name":"College of Medicine, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-0629","authenticated-orcid":false,"given":"Asif","family":"Naeem","sequence":"additional","affiliation":[{"name":"Department of Research labs, Research Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majed F.","family":"Alghoribi","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian","family":"Okdah","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maaweya E.","family":"Hamed","sequence":"additional","affiliation":[{"name":"College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad S.","family":"AlYami","sequence":"additional","affiliation":[{"name":"Pathology and Clinical Laboratory Medicine Administration, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athari","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"General Administration for Research and Studies, Ministry of Health, Riyadh 11176, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mushira","family":"Enani","sequence":"additional","affiliation":[{"name":"Medical Specialties Department, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, December 22). Coronavirus Disease 2019 (COVID-19): Situation Report, 33. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/331219."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1056\/NEJMe2001126","article-title":"Another Decade, Another Coronavirus","volume":"382","author":"Perlman","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Inf. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.3201\/eid2607.200885","article-title":"Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020","volume":"26","author":"Guo","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109781","DOI":"10.1016\/j.mehy.2020.109781","article-title":"Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission","volume":"141","author":"Correia","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maugeri, A., Barchitta, M., Battiato, S., and Agodi, A. (2020). Estimation of Unreported Novel Coronavirus (SARS-CoV-2) Infections from Reported Deaths: A Susceptible-Exposed-Infectious-Recovered-Dead Model. J. Clin. Med., 9.","DOI":"10.20944\/preprints202004.0052.v1"},{"key":"ref_10","unstructured":"European Centre for Disease Prevention and Control (2020, December 22). Novel Coronavirus Disease 2019 (COVID-19) Pandemic: Increased Transmission in the EU\/EEA and the UK\u2014Sixth update\u2014Stockholm: ECDC. Available online: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/RRA-sixth-update-Outbreak-of-novel-coronavirus-disease-2019-COVID-19.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"377","DOI":"10.15585\/mmwr.mm6913e1","article-title":"Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility\u2014King County, Washington, March 2020","volume":"69","author":"Kimball","year":"2020","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1126\/science.abb3221","article-title":"Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)","volume":"368","author":"Li","year":"2020","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.15585\/mmwr.mm6914e1","article-title":"Presymptomatic Transmission of SARS-CoV-2\u2014Singapore, 23 January\u201316 March 2020","volume":"69","author":"Wei","year":"2020","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3201\/eid2605.200146","article-title":"Risk for Transportation of Coronavirus Disease from Wuhan to Other Cities in China","volume":"26","author":"Du","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"362","DOI":"10.7326\/M20-3012","article-title":"Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review","volume":"173","author":"Oran","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1056\/NEJMc2001737","article-title":"SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients","volume":"382","author":"Zou","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22597","DOI":"10.1073\/pnas.2005476117","article-title":"Estimating unobserved SARS-CoV-2 infections in the United States","volume":"117","author":"Perkins","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1056\/NEJMc2009316","article-title":"Universal Screening for SARS-CoV-2 in Women Admitted for Delivery","volume":"382","author":"Sutton","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gianino, M.M., Politano, G., Scarmozzino, A., Stillo, M., Amprino, V., Di Carlo, S., Benso, A., and Zotti, C.M. (2019). Cost of Sickness Absenteeism during Seasonal Influenza Outbreaks of Medium Intensity among Health Care Workers. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16050747"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1056\/NEJMra021771","article-title":"How contagious are common respiratory tract infections?","volume":"348","author":"Musher","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_21","unstructured":"World Health Organization (2020, December 22). Coronavirus Disease 2019 (COVID-19): WHO COVID-19 Case Definition. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Surveillance_Case_Definition-2020.1."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41564-020-0713-1","article-title":"SARS-CoV-2 detection in patients with influenza-like illness","volume":"5","author":"Kong","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_23","unstructured":"Epidemiology Working Group for NCIP Epidemic Response, and Chinese Center for Disease Control and Prevention (2020). The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi, 41, 145\u2013151. (In Chinese)."},{"key":"ref_24","unstructured":"WHO (2020, December 22). Draft Landscape of COVID-19 Candidate Vaccines. Available online: https:\/\/www.who.int\/publications\/m\/item\/draft-landscape-of-covid-19-candidate-vaccines."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","article-title":"SARS-CoV-2 vaccines in development","volume":"586","author":"Krammer","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Laine, C., Cotton, D., and Moyer, D.V. (2020). COVID-19 Vaccine: Promoting Vaccine Acceptance. Ann. Intern. Med.","DOI":"10.7326\/M20-8008"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcv.2018.05.006","article-title":"Evaluation of Seegene Allplex Respiratory Panel 1 kit for the detection of influenza virus and human respiratory syncytial virus","volume":"105","author":"Gimferrer","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","article-title":"Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR","volume":"25","author":"Corman","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5144\/0256-4947.2020.1","article-title":"Hospital-based surveillance of influenza A(H1N1)pdm09 virus in Saudi Arabia, 2010\u20132016","volume":"40","author":"Abdalla","year":"2020","journal-title":"Ann. Saudi Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nature Methods."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence alignment\/map (SAM) format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rambaut, A., Holmes, E.C., O\u2019Toole, \u00c1., Hill, V., McCrone, J.T., Ruis, C., du Plessis, L., and Pybus, O.G. (2020). A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat. Microbiol.","DOI":"10.1101\/2020.04.17.046086"},{"key":"ref_35","first-page":"W5","article-title":"MAFFT-DASH: Integrated protein sequence and structural alignment","volume":"47","author":"Rozewicki","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_36","unstructured":"World Health Organization EMRO (2020, May 16). C Influenza (Seasonal). Available online: http:\/\/www.emro.who.int\/health-topics\/influenza\/influenza-updates.html."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1093\/bioinformatics\/bty407","article-title":"Nextstrain: Real-time tracking of pathogen evolution","volume":"34","author":"Hadfield","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_38","first-page":"13","article-title":"Complete Genome Sequence of the Sesbania Symbiont and Rice","volume":"1","author":"Rhizobium","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Naeem, A., Elbakkouri, K., Alfaiz, A., Hamed, M.E., Alsaran, H., AlOtaiby, S., Enani, M., and Alosaimi, B. (2020). Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015. J. Med. Virol., 11.","DOI":"10.1002\/jmv.25759"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1001\/jama.2020.2565","article-title":"Presumed Asymptomatic Carrier Transmission of COVID-19","volume":"323","author":"Bai","year":"2020","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0140-6736(20)31304-0","article-title":"Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): A population-based study","volume":"396","author":"Stringhini","year":"2020","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1056\/NEJMc2001468","article-title":"Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany","volume":"382","author":"Rothe","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1056\/NEJMc2013020","article-title":"Natural History of Asymptomatic SARS-CoV-2 Infection","volume":"383","author":"Sakurai","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1001\/jama.2020.8279","article-title":"Seroprevalence of SARS-CoV-2-Specific Antibodies Among Adults in Los Angeles County, California, on 10\u201311 April 2020","volume":"323","author":"Sood","year":"2020","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(20)31483-5","article-title":"Prevalence of SARS-CoV-2 in Spain (ENE-COVID): A nationwide, population-based seroepidemiological study","volume":"396","author":"Oteo","year":"2020","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"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","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1126\/science.abe1916","article-title":"Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Kenyan Blood Donors","volume":"371","author":"Uyoga","year":"2021","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1001\/jama.2020.4958","article-title":"Community Prevalence of SARS-CoV-2 Among Patients with Influenza like Illnesses Presenting to a Los Angeles Medical Center in March 2020","volume":"323","author":"Spellberg","year":"2020","journal-title":"JAMA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2020495","DOI":"10.1001\/jamanetworkopen.2020.20495","article-title":"Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children","volume":"3","author":"Song","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1016\/S0140-6736(20)31052-7","article-title":"SARS-CoV-2 and influenza virus co-infection","volume":"395","author":"Bodro","year":"2020","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/aje\/kwv452","article-title":"Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia","volume":"183","author":"Lessler","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1080\/22221751.2020.1785952","article-title":"Retrospective detection of SARS-CoV-2 in hospitalized patients with influenza-like illness","volume":"9","author":"Yu","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s41232-020-00126-7","article-title":"Genome evolution of SARS-CoV-2 and its virological characteristics","volume":"40","author":"Nakagawa","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_54","first-page":"2001200","article-title":"Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020","volume":"25","author":"Behillil","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"106006","DOI":"10.1016\/j.ijantimicag.2020.106006","article-title":"SARS-CoV-2 was already spreading in France in late December 2019","volume":"55","author":"Deslandes","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s11262-005-0070-4","article-title":"Amino acids 1 to 422 of the spike protein of SARS associated coronavirus are required for induction of cyclooxygenase-2","volume":"33","author":"Liu","year":"2006","journal-title":"Virus Genes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus","volume":"182","author":"Korber","year":"2020","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2020.07.012","article-title":"The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity","volume":"182","author":"Li","year":"2020","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1007\/s11481-020-09954-3","article-title":"Infectivity of SARS-CoV-2: There Is Something More than D614G?","volume":"15","author":"Kannan","year":"2020","journal-title":"J. Neuroimmune. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.virol.2004.01.004","article-title":"Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis","volume":"322","author":"Julias","year":"2004","journal-title":"Virology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0014-5793(95)00051-A","article-title":"Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase","volume":"359","author":"Fan","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e59633","DOI":"10.7554\/eLife.59633","article-title":"Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic","volume":"9","author":"Nelson","year":"2020","journal-title":"eLife"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:12:49Z","timestamp":1760159569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,19]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010136"],"URL":"https:\/\/doi.org\/10.3390\/v13010136","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,1,19]]}}}