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Global Efforts on Vaccines for COVID-19: Since, Sooner Or Later, We All Will Catch the Coronavirus

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Global Efforts on Vaccines for COVID-19: Since, Sooner Or Later, We All Will Catch the Coronavirus J Biosci (2020)45:68 Ó Indian Academy of Sciences DOI: 10.1007/s12038-020-00040-7 (0123456789().,-volV)(0123456789().,-volV) Review Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus RAJU MUKHERJEE Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, India (Email, [email protected]) MS received 3 April 2020; accepted 23 April 2020 COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet trans- mission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development. Keywords. COVID-19; SARS-CoV-2; coronavirus; vaccines 1. Introduction been neglecting emerging infectious disease areas. However, due to the present spread of the COVID-19 ‘Companies that have the skill to be able to do it are not pandemic, which has claimed, at the time of writing going to just sit around and have a warm facility, ready this article, 217,192 lives and infected 3,117,204 to go for when you need it’, said Anthony Fauci, the individuals so far, across all the continents except director of the National Institute of Allergy and Infec- Antarctica, the need for vaccines have rekindled new tious Diseases at NIH, USA, and a member of the interests and with a higher enthusiasm (Johns Hopkins White House Coronavirus Task Force, at a panel dis- University 2020). This can be understood from the cussion (Florko 2020). He has been aware of the mood rapidity in response to contain the outbreak and of vaccine-manufacturing Big Pharma, which has not designing modalities for treatment. According to changed much since the 1980s and is largely driven by reports from Institute Pasteur, Shanghai, the first notice a few very pertinent questions. Will the demand fade on treatments provided for pneumonia from hospitals away with the end of the outbreak? Will the people in Wuhan, China, was received on 30th December choose, sometimes due to foolish reasons of vaccine 2019. Within 8 days, the coronavirus was identified, hesitancy, not to use the product? What would be the and by 10th January 2020, the very first genome of the timeline to reach breakeven and create wealth? With virus was shared by the University of Sydney on behalf negligible prospects for profits, most drug makers have of the Chinese Academy of Sciences (Fontanet 2020; Huang et al. 2020). Consequent to that, a number of efforts are being made to socially contain the outbreak, This article is part of the Topical Collection: COVID-19: screen available drugs for repurposing for COVID-19 Disease Biology & Intervention. and design specific vaccines against the new http://www.ias.ac.in/jbiosci 68 Page 2 of 10 Raju Mukherjee coronavirus. This review highlights the genomic fea- serological diagnosis of asymptomatic spreaders, tures of coronavirus that should be considered for which are absent at the moment. However, here we will vaccine design, current innovations in vaccine tech- restrict our discussion to the multiple vaccines being nology, global efforts, and future challenges in vaccine developed against SARS-CoV-2. developments for COVID-19. 3. Origin of SARS-CoV-2 and genomic insights for vaccine development 2. COVID-19 and coronavirus From the entire initial set of five genome sequences COVID-19 is a new infectious disease of the respira- available, it was concluded that the new coronavirus is tory tract with chances of developing fulminant pneu- 99.9% identical among themselves, suggesting its monia similar to the severe acute respiratory syndrome recent entry into humans (Zhou et al. 2020). All the (SARS) and is caused by the new coronavirus (SARS- 3365 viral genomes known today form a tight cluster CoV-2), which spreads through contact with respiratory based on phylogeny and show evidences of only 20 droplets from nose and mouth (Chan et al. 2020; WHO mutational events, much lower than the expected rate 2020a). Notably, 80% of people who are exposed or of 10-4 substitutions per site per year. This slow evo- infected do not develop the active disease and show lution is despite carrying RNA as the genome and mild symptoms of seasonal flu and recover without much to the advantage for vaccine researchers (Dong major treatment. However, its estimated rate of inci- et al. 2020). The closest match with 88–96% overall dence is much higher and is in the range of 20–60% in identity is that of the bat-derived beta-coronaviruses, comparison with 8% for flu, and initial observations indicating a zoonotic origin of the disease, similar to concludes that those developing severe disease require SARS and MERS but genetically distinct from the hospitalization for a period twice as much as that for respective coronaviruses (Andersen et al. 2020). acute flu (Lenski 2020). It originated in the Hubei Interestingly, genomic and evolutionary evidence pla- province of China in late 2019, and spread rapidly ces the coronavirus found in Malayan pangolins around the world through human-to-human transmis- (Pangolin-CoV) as the next best match with greater sion along the international air-travel routes. The case than 91% identity, thus hinting at the anteater as a fatality rate for COVID-19 at the time of writing this possible intermediate host to the new coronavirus after article stands at 10 times more than 0.1%, as reported spillover from bats, like the palm civets and the dro- for the seasonal flu (Lenski 2020). SARS-CoV-2 is the medary camels in case of SARS-CoV and MERS-CoV, third member of the pathogenic coronavirus after respectively (Zhang et al. 2020). Further, the study SARS-CoV and MERS-CoV (causes the Middle East posits Pangolins-CoV as the possible common ancestor respiratory syndrome) that shows severe pathology in for the human and bat versions based on the key amino humans among few others that only cause mild clinical acid residues present in its surface protein and crucial symptoms like the flu (Cui et al. 2019). In the absence for interaction with the host receptor. Recombination of a clinically proven effective treatment regime, cur- events among the small sub-genomic regions are very rent therapies for COVID-19 mainly receive supportive common in coronaviruses due to the high level of co- care supplemented by different combinations of anti- infection that exists in their hosts. Therefore, tracing retroviral drugs. A few FDA approved drugs and the evolutionary history of coronaviruses can be quite immune therapies are being repurposed and currently challenging and debatable. in clinical trials at several stages and available only on Its positive-strand RNA genome consists of six compassionate grounds. They have been proven effi- major open reading frames and accessory genes coding cacious in controlling SARS, influenza, HIV, and the for the typical non-structural proteins, including the Ebola virus replication by either targeting the viral RNA-dependent RNA polymerase, proteases, and the RNA polymerase or the poly-protein protease or by structural proteins, including the matrix (M), envelope boosting host immunity as adjunct therapy (Harrison (E), spike (S) and nucleoprotein (N). The surface spike 2020). Convalescent plasma from recovered individu- (S) glycoprotein is responsible for binding to the als and monoclonal antibody therapies, which showed human cell surface receptor, followed by membrane some success during the Ebola outbreak in Western fusion and entry (figure 1) (de Wit et al. 2016). This Africa, are being developed (van Griensven et al. spike protein is also pivotal for determining host 2016). These antibodies will also form the basis for the specificity, estimating the capacity of disease Global efforts on vaccines for COVID-19 Page 3 of 10 68 Figure 1. Potential vaccine candidates under development for COVID-19 treatment. The potential targets for small molecule drugs under clinical trails are annotated with numbers. 1, Chloroquine (endosomal acidification inhibitor); 2, Lopinavir-Ritonavir (protease inhibitor); 3, Remdesevir (reverse transcriptase inhibitor). transmission, and for production of neutralizing anti- transfer much before November 2019 (Andersen et al. body in human. Generally, the spike protein of coron- 2020). An educated speculation indicates that a aviruses consists of a signal peptide, extracellular, COVID-19-type epidemic may recur at any time in the trans-membrane and intracellular regions. The host- future, by a different SARS-CoV-2 variant evolving recognizing extracellular domain, responsible for cell from the early isolates under selective pressure in membrane fusion, is divided by a polybasic cleavage animals, further emphasizing the need for a vaccine. site into a receptor binding S1 domain and the S2 domain (Andersen et al, 2020). When it comes to sequence identity at the amino acid level, which 4. Identifying potential targets for designing determines molecular recognition to the host receptor, vaccine candidates the S1 domain shows only 68% identity in comparison with the bat version. Expectedly, phylogenetic analysis Vaccination strategies can be effectively used to reduce also places the receptor binding domain to a lineage disease severity, control transmission by viral shedding closer to that of the SARS-CoV version, thus sug- and prevent future infections.
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