key: cord-350451-lf27iuwk authors: Benedetti, Francesca; Pachetti, Maria; Marini, Bruna; Ippodrino, Rudy; Ciccozzi, Massimo; Zella, Davide title: SARS‐CoV‐2: March toward adaptation date: 2020-07-11 journal: J Med Virol DOI: 10.1002/jmv.26233 sha: doc_id: 350451 cord_uid: lf27iuwk After an initial period of rising numbers of infected subjected by SARS-CoV-2 and deaths by COVID-19, currently some areas of the World are experiencing a reduction of cases. Different degrees of lockdown and social distancing measures greatly helped in limiting the spread of the disease. The contribution of other external factors like weather conditions and population density, though not as significant, seemed nonetheless to have played an additional role in shaping the course of the epidemic. A third factor still subject of debate is how and how much the mutations observed in SARS-CoV-2 provide an indication of viral fitness and adaptation, and their role first into the initial phases of transmission and now during the reduction of viral spreading. Aim of this commentary is to provide an overview of the status of the pandemic situation linking together the different factors implicated in current situation, and to summarize some strategies that could help us to better manage either a second wave of this virus or a potential new threat of similar nature. This article is protected by copyright. All rights reserved. The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human pathogen, first detected in China quickly became a global health emergency, culminating with the World Health Organization publicly proclaiming the SARS-CoV-2 outbreak as a pandemic (11 March 2020) . So far, more than 7 million people have been infected and more than 400 thousand have died, causing profound economic disruption and unsettling consolidated human traditions. SARS-CoV-2 is an enveloped +single-stranded RNA virus, belonging to the Betacoronavirus genus, which includes two other RNA viruses that have caused recent important epidemics: SARS caused by SARS-CoV and the Middle East respiratory syndrome (MERS) caused by MERS-CoV. SARS-CoV and MERS-CoV have caused more than 10 000 cumulative cases in the past 2 decades, with mortality rates of 9.6% for SARS-CoV and 37% for MERS-CoV, respectively. [1] [2] [3] [4] Viral fitness of RNA viruses is influenced by their very high frequency of mutation, which, in turn, can affect infection speed and evolution rate. 5 However, the resulting genetic variability needs to be balanced between the maintenance of genetic information integrity and survival within the host. [6] [7] [8] The viral genome mutagenic process is depended on several factors, including viral enzymes responsible for nucleic acids replication, which may have few or no proofreading and/or postreplicative nucleic acid repair capability. In addition, host enzymes, spontaneous nucleic acid damages due to physical and chemical mutagens, and recombination events can contribute to the genomic variability, together with particular genetic elements responsible for the production of new variants. Mutation rates are modulated also by additional factors such as determinants of the template sequence and structure involved in viral replication. 5 In most viruses, RNA polymerase lacks proofreading capability, with some exceptions such as Nidovirales order (to which the Betacororonavirus belongs). In Nidoviruses, complex machinery originated as cleavage products of the viral ORF1a and ORF1b, composed of a polymerase (RNA-depended RNA polymerase) and nonstructural proteins, is responsible for virus replication and transcription. 9,10 Biological characterization of viral mutations provide precious insights for assessing viral drug resistance, immune escape, and pathogenesis-related mechanisms. In addition, viral mutation studies are crucial for designing new vaccines, antiviral drugs, and diagnostic assays. Several reports result show that SARS-CoV-2 is rapidly moving across countries, and new mutation hotspots are emerging in different parts of the genome. [11] [12] [13] [14] [15] [16] [17] [18] Such variability indeed has implications for control of the pandemic and potential emergence of viral strains with different characteristics, including increased or reduced infectivity and lethality. Although SARS-CoV-2 is less lethal than MERS-CoV, up to 20% of the infected people develop rapidly a severe disease characterized by interstitial pneumonia and acute respiratory distress syndrome that can ultimately lead to death. This is particularly evident in elderly and in people with underlying medical conditions. 19 However, most of the patients remain asymptomatic or develop mild symptoms, like fever and dry From a public health perspective, these data are important in the case SARS-CoV-2 reemerges in late fall or early winter of 2020, or another respiratory virus appears in the distant future. Timely viral detection, more precise, and reliable tracking methods leading to swift isolation of exposed and infected subjects together with the prompt implementation of measures of social distancing may be complemented with weather pattern analysis and viral sequence analysis, to help to shape more focused interventions for the quick recognition and early containment of new emerging clusters of infection. The authors declare that there are no conflict of interests. http://orcid.org/0000-0003-3866-9239 Davide Zella http://orcid.org/0000-0001-5576-5770 A novel coronavirus associated with severe acute respiratory syndrome Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome Identification of a novel coronavirus in patients with severe acute respiratory syndrome Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group Why are RNA virus mutation rates so damn high? 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Environ Microbiol SARS-CoV-2: March toward adaptation