key: cord-1010478-nody2lj2 authors: Kirola, Laxmi title: Genetic emergence of B.1.617.2 in COVID-19 date: 2021-07-24 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2021.100929 sha: e9497e386836f77e15148d3f007e29fddc6fbf0f doc_id: 1010478 cord_uid: nody2lj2 Many proactive steps have been taken worldwide to fight against SARS-CoV-2 pandemic and to prevent COVID-19 spread with realistic approaches. Recently, a novel variant B.1.617.2 has been identified in India which is rapidly transmitting to other countries. Challenging, current therapeutics, wide vaccination and future research in COIVD-19. The Indian SARS-CoV-2 Consortium on Genomics ( http://dbtindia.gov.in/insacog) includes 10 different national laboratories within the country and this group is continuing the sequencing process to map the complete genetic code of COVID-19 virus. COVID-19, a corona virus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported on December 2019 in Wuhan China [1] . The D614G was first identified in SARS-CoV-2 which was dominated later to other countries and across the world during the first wave of Subsequently, many other variants of SARS-CoV-2 has been identified worldwide and a few of them are classified as variants of concern (VOC), variants of interest (VOI), and variants of high consequence by the Centers for Disease Control and Prevention [2] . As of June 12, 2021, ~175 million cases of COVID-19 have been reported, with ~3.79 million total deaths and an increasing number of recovering cases of >94 million; perhaps, these numbers could be substantially underestimated. Three different VOCs namely B.1.1.7, B.1.351, and P.1 were initially prevalent within the United Kingdom (UK), South Africa, and Brazil, respectively and subsequently worldwide [3] . In addition, VOIs such as B.1.617 and B.1.618 have emerged in India and recently B.1.617.2 (also known as the Delta variant), a sub lineage of B.1.617 is continuously transmitting at a higher rate within the country and across the world [4] . Therefore, this is confirmed as a VOC by World Health Organization [5] and this could be possibly linked with the second wave of COVID-19 in India [6] . Nevertheless, E484Q mutation was seen first time in the B.1.351 and P.1 which was substituted later to E484K, thus, this had emerged independently several times in other populations [7] . This simple process discloses that the virus mutates within its own family or creates new lineages to J o u r n a l P r e -p r o o f function as a VOC. The B.1.427/B.1.429 lineages have such VOC called L452R mutation (first identified in the USA) and this has been shown to be almost >20% higher transmissibility in comparison to preexisting reported variants [8] . Besides, B.1.617.2 is transmitting much rapidly in Indian population and recently this variant has been seen in many other countries [4] . A recent study has shown variant B.1.1.7 is 43% to 90% more transmissible in comparison to preexisting lineages in European population as well as in other countries [9] . The initial GISAID data This observation further confirms a higher relative abundance of Delta variant worldwide. Many studies have exhibited an amino acid change inside 438-506 position in the Spike protein (also called receptor-binding domain) could be considerably associated with increase in virus transmission, infection, or evade immunity [12] . Further, both E484Q and L452R amino acid substitutions are present within the receptor-binding domain (RBD) of the spike protein like most other VOCs [13] . For example, L452R mutation could be involved in enhanced interaction with human angiotensin-converting enzyme 2 (ACE2) receptor of the spike protein of COVID-19 and most probably leading to increased rate of infection [14] . Moreover, other mutations such as E484K/E484Q increase the binding affinity through altering electrostatic interactions, while, at the same time, to create newer hydrogen bondings [15] . In addition, the N501Y increases stronger hydrophobic interactions of RBD-ACE2 and produces more hydrogen-bonding J o u r n a l P r e -p r o o f networks [16] . The K417N implicates this interaction of RBD binding to ACE2 alone or with N501Y and E484K together and improves overall binding affinity of this complex [15, 16] . Last but not the least, the D614G mutation stabilizes the spike protein for efficient entry within the host cell [17] . Table 1 . Furthermore, B.1.617.2 which contains these two mutations also leads to increase in virulence by reducing the antibody binding affinity as well as immune evasion [18] . Now, B.1.617.2 becomes an important variant in Indian context as it appears with an increasing prevalence from just 1% to 70% within the months of March to May 2021 [19] . Instead, the B.1.1.7 had already dominated in Britain and >114 countries including India [9] . Nonetheless, the latest data on GISAID shows B. Ireland indicate a higher rate of severe disease transmission, hospitalization and increased risk for emergence attention in individuals carrying the Delta variant [5] . Interestingly, in a secondary analysis which was performed in the United Kingdom (29 March-11 May 2021), uncovered J o u r n a l P r e -p r o o f higher attack rate among cases with Delta variant [5] . The B.1.617.2 is likely to have a selective advantage over other lineages for such a short period of increased transmissibility, infectivity or possibly escape from natural immunity [20] [21] [22] . Currently, many lineages are circulating at this time in India and worldwide, the rapid expansion of B.1.617.2 (Delta variant) over other lineages could be possibly due to natural selection and genetic displacement of SARS-CoV-2 genome [19, 23] . Interestingly, a latest study has investigated the variant B.1.617+ with mutations (L452R, E484Q and P681R) in different other combinations, and showed this barely affecting the efficiency of cellular entry and to elude immunity when elicited with neutralizing antibodies and BNT162b2 mRNA vaccine. Further, they described that the mutation P681R which contributes to increased pathogenesis through syncytium formation as observed in hamsters and also in humans for higher infected growth rate in India [24] . Conversely, a recent study from India has shown a likely equal neutralizing capacity for B.1.617 among the vaccinated individuals versus the recovered COVID-19 patients [25] . at least to answer further robust questions and provide accurate information in the framework settings (e.g., policy recommendations, managing current and future VOC and overall staying ahead of next pandemic). Furthermore, the dynamic virulency of SARS-CoV-2 challenges to develop next-generation vaccines, better genomic services and surveillances which can help us to save the humanity against future corona virus. All the survey analysis, review writing, and editing were conducted by LK. LK approved the final manuscript. 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