Role of available COVID-19 vaccines in reducing deaths and perspective for next generation vaccines and therapies to counter emerging viral variants: an update.

The COVID-19 disease wreaked havoc all over the world causing more than 6 million deaths out of over 519 million confirmed cases. It not only disturbed the human race health-wise but also caused huge economic losses and social disturbances. The utmost urgency to counter pandemic was to develop effective vaccines as well as treatments that could reduce the incidences of infection, hospitalization and deaths. The most known vaccines that could help in managing these parameters are Oxford-AstraZeneca (AZD1222), Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) and Johnson & Johnson (Ad26.COV2.S). The effectiveness of AZD1222 vaccine in reducing deaths is 88% in the age group 40-59 years, touching 100% in the age group 16-44 years & 65-84 years. BNT162b2 vaccine also did well in reducing deaths due to COVID-19 (95% in the age group 40-49 years and 100% in the age group 16-44 years. Similarly, mRNA-1273 vaccine showed potential in reducing COVID-19 deaths with effectiveness ranging from 80.3 to 100% depending upon age group of the vaccinated individuals. Ad26.COV2.S vaccine was also 100% effective in reducing COVID-19 deaths. The SARS-CoV-2 emerging variants have emphasized the need of booster vaccine doses to enhance protective immunity in vaccinated individuals. Additionally, therapeutic effectiveness of Molnupiravir, Paxlovid and Evusheld are also providing resistance against the spread of COVID-19 disease as well as may be effective against emerging variants. This review highlights the progress in developing COVID-19 vaccines, their protective efficacies, advances being made to design more efficacious vaccines, and presents an overview on advancements in developing potent drugs and monoclonal antibodies for countering COVID-19 and emerging variants of SARS-CoV-2 including the most recently emerged and highly mutated Omicron variant.

Comprehensive deep mutational scanning reveals the pH induced stability and binding differences between SARS-CoV-2 spike RBD and human ACE2.

The SARS-CoV-2 spike (S) glycoprotein with its mobile receptor-binding domain (RBD), binds to the human ACE2 receptor and thus facilitates virus entry through low-pH-endosomal pathways. The high degree of SARS-CoV-2 mutability has raised concern among scientists and medical professionals because it created doubt about the effectiveness of drugs and vaccinations designed specifically for COVID-19. In this study, we used computational saturation mutagenesis approach, including structure-based free energy calculations to analyse the effects of the missense mutations on the SARS-CoV-2 S-RBD stability and the S-RBD binding affinity with ACE2 at three different pH (pH 4.5, pH 6.5, and pH 7.4). A total of 3705 mutations in the S-RBD protein were analyzed, and we discovered that most of these mutations destabilize the RBD protein. Specifically, residues G404, G431, G447, A475, and G526 were important for RBD protein stability. In addition, RBD residues Y449, Y489, Y495, Q498, and N487 were critical for the RBD-ACE2 interaction. Next, we found that the distribution of the mean stability changes and mean binding energy changes of RBD due to mutations at both serological and endosomal pH correlated well, indicating the similar effects of mutations. Overall, this computational analysis is useful for understanding the effects of missense mutations in SARS-CoV-2 pathogenesis at different pH.Communicated by Ramaswamy H. Sarma.

Hopelessness among Medical Students Caused Due to COVID-19 Pandemic Linked Educational Hiatus: A Case Study of Bursa Uludag University, Tü,rkiye

The COVID-19 pandemic has caused disruptions in medical education, leading to feelings of hopelessness among students regarding their medical careers. However, effective institutional crisis-response approaches can mitigate these feelings of hopelessness. This study evaluated changes in the levels of hopelessness among Turkish medical students due to interruptions in their education caused by the pandemic between March and July 2020, using the Beck Hopelessness Scale in three selected periods. A statistical survey was conducted with a total of 3580 participants in three different periods to study the impact of various contributing factors, such as socio-economic status, family problems, health problems, and lack of working environment, on the levels of hopelessness in conjunction with active COVID-19 cases and the effect of institutional interventions for the continuation of medical education during the pandemic. The analysis revealed a direct relationship between contributing factors and hopelessness scores at the end of the selected three periods. Additionally, active COVID-19 cases and institutional crisis-response strategies were found to be indirectly associated with students' hopelessness. An increase in students' hopelessness was found to be related to an increase in active COVID-19 cases in the country, a lack of continuing education practices, and the role of contributing factors. Conversely, a decrease in hopelessness was associated with effective institutional crisis-response strategies. These findings suggest that educational settings dealing with practical subjects should prioritize preparedness for crisis situations.

In silico identification of microRNAs targeting the PPARα/γ: promising therapeutics for SARS-CoV­2 infection.

The SARS-CoV-2 lifecycle is dependent on the host metabolism machinery. It upregulates the PPARα and PPARγ genes in lipid metabolism, which supports the essential viral replication complex including lipid rafts and palmitoylation of viral protein. The use of PPAR ligands in SARS-CoV-2 infection may have positive effects by preventing cytokine storm and the ensuing inflammatory cascade. The inhibition of PPARα and PPARγ genes may alter the metabolism and may disrupt the lifecycle of SARS-CoV-2 and COVID-19 progression. In the present work, we have identified possible miRNAs targeting PPARα and PPARγ in search of modulators of PPARα and PPARγ genes expression. The identified miRNAs could possibly be viewed as new therapeutic targets against COVID-19 infection.

Energetic and frustration analysis of SARS-CoV-2 nucleocapsid protein mutations.

The ongoing COVID-19 spreads worldwide with the ability to evolve in diverse human populations. The nucleocapsid (N) protein is one of the mutational hotspots in the SARS-CoV-2 genome. The N protein is an abundant RNA-binding protein critical for viral genome packaging. It comprises two large domains including the N-terminal domain (NTD) and the C-terminal domain (CTD) linked by the centrally located linker region. Mutations in N protein have been reported to increase the severity of disease by modulating viral transmissibility, replication efficiency as well as virulence properties of the virus in different parts of the world. To study the effect of N protein missense mutations on protein stability, function, and pathogenicity, we analyzed 228 mutations from each domain of N protein. Further, we have studied the effect of mutations on local residual frustration changes in N protein. Out of 228 mutations, 11 mutations were predicted to be deleterious and destabilized. Among these mutations, R32C, R191C, and R203 M mutations fall into disordered regions and show significant change in frustration state. Overall, this work reveals that by altering the energetics and residual frustration, N protein mutations might affect the stability, function, and pathogenicity of the SARS-CoV-2.

In silico evaluation of the inhibitory potential of nucleocapsid inhibitors of SARS-CoV-2: a binding and energetic perspective.

The COVID-19 outbreak brought on by the SARS-CoV-2 virus continued to infect a sizable population worldwide. The SARS-CoV-2 nucleocapsid (N) protein is the most conserved RNA-binding structural protein and is a desirable target because of its involvement in viral transcription and replication. Based on this aspect, this study focused to repurpose antiviral compounds approved or in development for treating COVID-19. The inhibitors chosen are either FDA-approved or are currently being studied in clinical trials against COVID-19. Initially, they were designed to target stress granules and other RNA biology. We have utilized structure-based molecular docking and all-atom molecular dynamics (MD) simulation approach to investigate in detail the binding energy and binding modes of the different anti-N inhibitors to N protein. The result showed that five drugs including Silmitasterib, Ninetanidinb, Ternatin, Luteolin, Fedratinib, PJ34, and Zotatafin were found interacting with RNA binding sites as well as to predicted protein interface with higher binding energy. Overall, drug binding increases the stability of the complex with maximum stability found in the order, Silmitasertib > PJ34 > Zotatatafin. In addition, the frustration changes due to drug binding brings a decrease in local frustration and this decrease is mainly observed in α-helix, ß3, ß5, and ß6 strands and are important for drug binding. Our in-silico data suggest that an effective interaction occurs for some of the tested drugs and prompt their further validation to reduce the rapid outspreading of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Bacterial co-infections and antimicrobial resistance associated with the Coronavirus Disease 2019 infection.

Bacterial co-infections are typically associated with viral respiratory tract infections and pose a significant public health problem around the world. COVID-19 infection damages tissues lining the respiratory track and regulates immune cells/cytokines leading to microbiome dysbiosis and facilitating the area to be colonized by pathogenic bacterial agents. There have been reports of different types of bacterial co-infection in COVID-19 patients. Some of these reports showed despite geographical differences and differences in hospital settings, bacterial co-infections are a major cause of morbidity and mortality in COVID-19 patients. The inappropriate use of antibiotics for bacterial infections, particularly broad-spectrum antibiotics, can also further complicate the infection process, often leading to multi drug resistance, clinical deterioration, poor prognosis, and eventually death. To this end, researchers must establish a new therapeutic approach to control SARS-CoV-2 and the associated microbial coinfections. Hence, the aim of this review is to highlight the bacterial co-infection that has been recorded in COVID-19 patients and the status of antimicrobial resistance associated with the dual infections.

SARS-CoV-2 origins: zoonotic Rhinolophus vs contemporary models.

The question of the origin of coronavirus spread like wildfire ever since it wreaked havoc among humankind, and ever since the scientific community has worked tirelessly to trace the history of the virus. In this review, we have tried to compile relevant literature pertaining to the different theories of origin of SARS-CoV-2, hopefully without any bias, and we strongly support the zoonotic origin of the infamous SARS-CoV-2 in bats and its transfer to human beings through the most probable evolutionary hosts, pangolins and minks. We also support the contemporary 'Circulation Model' that simply mirrors the concept of evolution to explain the origin of the virus which, the authors believe, is the most rational school of thought. The most recent variant of SARS-CoV-2, Omicron, has been taken as an example to clarify the concept. We recommend the community to refer to this model for further understanding and delving deep into this mystery of the origin of SARS-CoV-2.

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin.

Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer's and Parkinson's diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.

Silybin B and Cianidanol Inhibit Mpro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies.

BACKGROUND: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2. METHODS: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41). RESULTS: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces. CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.

Egypt's COVID-19 Recent Happenings and Perspectives: A Mini-Review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected countries across the world. While the zoonotic aspects of SARS-CoV-2 are still under investigation, bats and pangolins are currently cited as the animal origin of the virus. Several types of vaccines against COVID-19 have been developed and are being used in vaccination drives across the world. A number of countries are experiencing second and third waves of the pandemic, which have claimed nearly four million lives out of the 180 million people infected globally as of June 2021. The emerging SARS-CoV-2 variants and mutants are posing high public health concerns owing to their rapid transmissibility, higher severity, and in some cases, ability to infect vaccinated people (vaccine breakthrough). Here in this mini-review, we specifically looked at the efforts and actions of the Egyptian government to slow down and control the spread of COVID-19. We also review the COVID-19 statistics in Egypt and the possible reasons behind the low prevalence and high case fatality rate (CFR%), comparing Egypt COVID-19 statistics with China (the epicenter of COVID-19 pandemic) and the USA, Brazil, India, Italy, and France (the first countries in which the numbers of patients infected with COVID-19). Additionally, we have summarized the SARS-CoV-2 variants, vaccines used in Egypt, and the use of medicinal plants as preventive and curative options.

Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents.

BACKGROUND: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. METHODS: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. RESULTS: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. CONCLUSION: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.

Neutralization of SARS-CoV-2 Spike Protein via Natural Compounds: A Multilayered High Throughput Virtual Screening Approach.

BACKGROUND: Previously human society has faced various unprecedented pandemics in the history and viruses have majorly held the responsibilities of those outbreaks. Furthermore, due to amplified global connection and speedy modernization, epidemic outbreaks caused by novel and re-emerging viruses signify potential risk to community health. Despite great advancements in immunization and drug discovery processes, various viruses still lack prophylactic vaccines and efficient antiviral therapies. Although, vaccine is a prophylaxes option, but it cannot be applied to infected patients, hence therapeutic interventions are urgently needed to control the ongoing global SARS- CoV-2 pandemic condition. To spot the novel antiviral therapy is of decisive importance and Mother Nature is an excellent source for such discoveries. METHODOLOGY: In this article, prompt high through-put virtual screening for vetting the best possible drug candidates from natural compounds' databases has been implemented. Herein, time tested rigorous multi-layered drug screening process to narrow down 66,969 natural compounds for the identification of potential lead(s) is implemented. Druggability parameters, different docking approaches and neutralization tendency of the natural products were employed in this study to screen the best possible natural compounds from the digital libraries. CONCLUSION: The results of this study conclude that compounds PALA and HMCA are potential inhibitors of SARS-CoV-2 spike protein and can be further explored for experimental validation. Overall, the methodological approach reported in this article can be suitably used to find the potential drug candidates against SARS-CoV2 in the burning situation of COVID-19 with less expenditure and a concise span of time.

MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges.

The Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.

In Silico Studies Reveal Antiviral Effects of Traditional Indian Spices on COVID-19.

BACKGROUND: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (Mpro) play a significant role in infection development were considered as potential drug targets. METHODS: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with Mpro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR). RESULTS: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and Mpro of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against Mpro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces. CONCLUSION: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.

Recent advances in vaccine and immunotherapy for COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of cases and hundreds of thousands of deaths. Beyond there being no available antiviral therapy, stimulating protective immunity by vaccines is the best option for managing future infections. Development of a vaccine for a novel virus is a challenging effort that may take several years to accomplish. This mini-review summarizes the immunopathological responses to SARS-CoV-2 infection and discusses advances in the development of vaccines and immunotherapeutics for COVID-19.

Genomic Epidemiology and Recent Update on Nucleic Acid-Based Diagnostics for COVID-19.

Purpose of the Review: The SARS-CoV-2 genome has been sequenced and the data is made available in the public domain. Molecular epidemiological investigators have utilized this information to elucidate the origin, mode of transmission, and contact tracing of SARS-CoV-2. The present review aims to highlight the recent advancements in the molecular epidemiological studies along with updating recent advancements in the molecular (nucleic acid based) diagnostics for COVID-19, the disease caused by SARS-CoV-2. Recent Findings: Epidemiological studies with the integration of molecular genetics principles and tools are now mainly focused on the elucidation of molecular pathology of COVID-19. Molecular epidemiological studies have discovered the mutability of SARS-CoV-2 which is of utmost importance for the development of therapeutics and vaccines for COVID-19. The whole world is now participating in the race for development of better and rapid diagnostics and therapeutics for COVID-19. Several molecular diagnostic techniques have been developed for accurate and precise diagnosis of COVID-19. Summary: Novel genomic techniques have helped in the understanding of the disease pathology, origin, and spread of COVID-19. The whole genome sequence established in the initial days of the outbreak has enabled to identify the virus taxonomy. Several rapid, accurate, and sensitive diagnostic methods have been developed; those are based on the principle of detecting SARS-CoV-2 nucleic acids in clinical samples. Most of these molecular diagnostics are based on RT-PCR principle.

SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China, which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 210 countries while affecting more than 25 million people and causing more than 843,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia, and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs, and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. To date, August 30, 2020, no effective, proven therapeutic antibodies or specific drugs, and vaccines have turned up. In this review article, we describe the underlying molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview

The recent outbreak of SARS-CoV-2 that started in Wuhan, China, has now spread to several other countries and is in its exponential phase of spread. Although less pathogenic than SARS-CoV, it has taken several lives and taken down the economies of many countries. Before this outbreak, the most recent coronavirus outbreaks were the SARS-CoV and the MERS-CoV outbreaks that happened in China and Saudi Arabia, respectively. Since the SARS-CoV-2 belongs to the same family as of SARS-CoV and MERS-CoV, they share several similarities. So, this review aims at understanding the new scenario of SARS-CoV-2 outbreak and compares the epidemiology, clinical presentations, and the genetics of these coronaviruses. Studies reveal that SARS-CoV-2 is very similar in structure and pathogenicity with SARS-CoV, but the most important structural protein, i.e., the spike protein (S), is slightly different in these viruses. The presence of a furin-like cleavage site in SARS-CoV-2 facilitates the S protein priming and might increase the efficiency of the spread of SARS-CoV-2 as compared to other beta coronaviruses. So, furin inhibitors can be targeted as potential drug therapies for SARS-CoV.