In Search of Novel Coronavirus 19 Therapeutic Targets
amith kumar2020, HELIX
Sign up for access to the world's latest research
checkGet notified about relevant papers
checkSave papers to use in your research
checkJoin the discussion with peers
checkTrack your impact
Abstract
Novel Coronavirus 2019 pandemic has become a nightmare of the year 2019-20. It is affecting both health and wealth across the world. It has become a great challenge for the entire human race to protect itself from the viral outbreak. This is time for the entire Scientific community to come together and undertake studies and contribute in conducting research on CoVID 19 and possible solutions to defeat this killer, million times smaller than humans, as even minute information can also play a very important role in fighting against the Virus. The current work is aimed to analyze the genome of CoVID 19 and compare its evolutionary relation with the other species of viruses that are known to cause respiratory disorders. Viral membrane proteins and proteins involved in replication of viral genetic material play an integral part in virushost interactions. These classes of protein are often the best candidates for antiviral drug and vaccine targets. Disrupting these proteins may be an effective means to inhibit the growth and disintegrate the virus. Taking advantage of the recent release of some of the gene sequences and the genome of Novel Coronavirus 2019 by NCBI GenBank and the agility provided by Insilico Bioinformatics tools, the current work aimed to study the evolutionally conserved regions of the genome of the CoVid 19. The comparison of the complete genome and specifically the coding gene sequence for membrane proteins and proteins involved in viral replication of MN908947.3 Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome-2019 (better known as Covid 19), Isolated from China, was conducted. 25 viruses including commonly known respiratory tract pathogen were selected for the current study. Sequence similarity analysis and comparative study results revealed that the viral membrane protein, M protein Shares similarity only with the other corona group of viruses and (MERS) and not with HCOV. Moreover, the complete genome comparison revealed the presence of a specific conserved gene region shared by MERS and CoVid 19, which was further analyzed. Identifying the commonly shared gene regions can immensely aid in identifying druggable target and help in development of appropriate therapy protocol or medication for 2019 novel Coronavirus.
Related papers
Sequence and structural analysis of COVID-19 E and M proteins with MERS virus E and M proteins—A comparative study
Biochemistry and biophysics reports, 2021
has demonstrated that Coronaviruses are capable of causing primary lethal infections in humans, and the pandemic is now a global concern. The COVID-19 belongs to the beta coronavirus family encoding 29 proteins, of which four are structural, the Spike, Membrane, Envelope, and Nucleocapsid proteins. Here we have analyzed and compared the Membrane (M) and Envelope (E) proteins of COVID-19 and MERS with SARS and Bat viruses. The sequence analysis of conserved regions of both E and M proteins revealed that many regions of COVID-19 are similar to Bat and SARS viruses while the MERS virus showed variations. The essential binding motifs found in SARS appeared in COVID-19. Besides, the M protein of COVID-19 showed a distinct serine phosphorylation site in the C-terminal domain, which looked like a catalytic triad seen in serine proteases. A Dileucine motif occurred many times in the sequence of the M protein of all the four viruses compared. Concerning the structural part, the COVID-19 E protein showed more similarity to Bat while MERS shared similarity with the SARS virus. The M protein of both COVID-19 and MERS displayed variations in the structure. The interaction between M and E proteins was also studied to know the additional binding regions. Our study highlights the critical motifs and structural regions to be considered for further research to design better inhibitors for the infection caused by these viruses.
Sequence and Structural Analysis of COVID-19 E and M Protein With MERS Virus E and M Protein – A Comparative Study
Biochemistry and Biophysics Reports, 2020
The outbreak of SARS in 2003, MERS in 2012, and now COVID-19 in 2019 have demonstrated that Coronaviruses are capable of causing primary lethal infections in humans, and the pandemic is now a global concern The COVID-19 belongs to the beta coronavirus family encoding 29 proteins, of which four are structural, the Spike, Membrane, Envelope, and Nucleocapsid proteins Here we have analyzed and compared the Membrane (M) and Envelope (E) proteins of COVID-19 and MERS with SARS and Bat viruses The sequence analysis of conserved regions of both E and M protein revealed that many regions of COVID-19 are similar to Bat and SARS viruses while the MERS virus showed variations The essential binding motifs found in SARS appeared in COVID-19 Besides, the M protein of COVID-19 showed a distinct serine phosphorylation site in the C-terminal domain, which looked like a catalytic triad seen in serine proteases A Dileucine motif occurred many times in the sequence of the M protein of all the four viru...
A review of novel coronavirus disease (COVID-19): based on genomic structure, phylogeny, current shreds of evidence, candidate vaccines, and drug repurposing
3 Biotech
Coronavirus disease (COVID-19) pandemic is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 13, 2021, more than 118.9 million cases were infected with COVID-19 worldwide. SARS-CoV-2 is a positive-sense single-stranded RNA beta-CoV. Most COVID-19 infected individuals recover within 1-3 weeks. Nevertheless, approximately 5% of patients develop acute respiratory distress syndrome and other systemic complications, leading to death. Structural genetic analyses of SARS-CoV-2 have shown genomic resemblances but a low evolutionary correlation to SARS-CoV-1 responsible for the 2002-2004 outbreak. The S glycoprotein is critical for cell adhesion and the entrance of the virus into the host. The process of cell entry uses the cellular receptor named angiotensin-converting enzyme 2. Recent evidence proposed that the CD147 as a SARS-CoV-2′s potential receptor. The viral genome is mainly held by two nonstructural proteins (NSPs), ORF1a and ORF1ab, along with structural proteins. Although NSPs are conserved among the βCoVs, mutations in NSP2 and NSP3 may play critical roles in transmitting the virus and cell tropism. To date, no specific/ targeted anti-viral treatments exist. Notably, more than 50 COVID-19 candidate vaccines in clinical trials, and a few being administered. Preventive precautions are the primary strategy to limit the viral load transmission and spread, emphasizing the urgent need for developing significant drug targets and vaccines against COVID-19. This review provides a cumulative overview of the genomic structure, transmission, phylogeny of SARS-CoV-2 from Indian clusters, treatment options, updated discoveries, and future standpoints for COVID-19.
Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design
2020
Novel coronavirus has wrecked medical and health care facilities claiming ~5% death tolls globally. All efforts to contain the pathogenesis either using inhibitory drugs or vaccines largely remained futile due to a lack of better understanding of the genomic feature of this virus. In the present study, we compared the 2019-nCoV with other coronaviruses, which indicated that bat-SARS like coronavirus could be a probable ancestor of the novel coronavirus. The protein sequence similarity of pangolin-hCoV and bat-hCoV with human coronavirus was higher as compared to their nucleotide similarity denoting the occurrence of more synonymous mutations in the genome. Phylogenetic and alignment analysis of 591 novel coronaviruses of different clades from Group I to Group V revealed several mutations and concomitant amino acid changes. Detailed investigation on nucleotide substitution unfolded 100 substitutions in the coding region of which 43 were synonymous and 57 were of non-synonymous type. ...
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding
The Lancet, 2020
Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99•98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensinconverting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.
Novel Coronavirus (SARS-COV-2): Molecular Biology, Pathogenesis, Pathobiology and Advances in Treatment of COVID-19 Patients– an Update
Journal of Experimental Biology and Agricultural Sciences, 2020
The novel coronavirus (CoV), earlier named 2019-nCoV, and later as severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) has now created havoc and panic across the globe by its severe ongoing pandemic. This virus has to date as of 23rd November 2020, killed nearly 1.4 million persons out of more than 59 million confirmed positive cases, while spreading rapidly in more than 215 countries and territories. Taxonomically, SARS-CoV-2 has been characterized in genus Betacoronavirus, which contains non-segmented positive-sense, single-stranded (ss) RNA genome of 30 kb. The first two open reading frames (ORFs), ORF1a and ORF1b, of SARS-CoV-2, encode 16 non-structural proteins (nsp1-nsp16), whereas other ORFs encodes four main structural proteins (sp) [spike (s) by ORF2, envelope (E) by ORF4, membrane (M) by ORF5, nucleoprotein (N) by ORF9], and accessory proteins essential for the virus fitness, pathogenesis and host immunity evasion. Sequence alignments of SARS-CoV-2 with genomes...
Genomics-led insight into the coronavirus evolution, pathogenicity and management
Annals of Phytomedicine: An International Journal, 2021
Coronavirus disease 2019 (COVID-19) has so far been the most devastating pandemic ever faced by mankind. Caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the disease is becoming deadly due to frequent emergence of variants. The virus belongs to the group, Betacoronaviruses, and shares more than 90% amino acid identity with SARS-CoV. The SARS-CoV-2 possess a single-stranded positive-sense RNA which is the largest known viral RNA genome consisting of 25,000-30,000 nucleotides with 14 ORFs. The 3'-region of the genome harbours four structura l proteins, namely; the spike, nucleocapsid, envelope and the membrane proteins; the S protein plays the most important role during infection. Genomics-led studies are prerequisites to understand the pathogenicity of any pathogen and for devising its management strategies. The availability of SARS-CoV-2 sequence data and suitable bioinformatics platforms have allowed researchers to identify potential therapeutic targets and to predict immune response for accelerating therapeutics and vaccine development. A plethora of such options are available tha t inclu des repurposing existing drugs, monoclonal antibodies, anti-inflammatory agents, etc. Moreover, different types of vaccines such as mRNA-based, viral vector, inactivated virus, etc., with different efficacy levels have been approved. However, their efficacy might get compromised with time, particularly due to frequent mutations in the viral genomes. Here, we provide a comprehensive insight into the genome structure, evolution, pathogenicity as well as the achieved success and limitations in management of this notorious virus.
A Spotlight on Novel Coronavirus (COVID – 19) with Various Types of Strains
International Journal of Life Science and Pharma Research
Deadly COVID-19 viruses have raised a pandemic situation in the year 2019, causing serious and contagious respiratory infections in humans. SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the main causative agent for this disease outbreak. The pandemic created a critical impact on the global economy. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis that lasted about 11 months. Since, late 2020, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations. This resulted so far, in over 2.7 million deaths and near about 122 million infection cases. Most mutations in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome are either deleterious and swiftly purged or relatively neutral. As far as the concern is the variants it impacts the virus characteristics, including antigenicity and transmissibility in response to the modification of the human immune profile. In recent days, COVID-...
Review on Newly Identified Coronavirus and its Genomic Organization
SSR Institute of International Journal of Life Sciences, 2020
Human Coronaviruses (HCoV) exhibit positive single stranded RNA genome with enveloped nucleocapsid. Coronavirus belongs to the family Coronaviridae, originated from avian and mammalian species causes upper respiratory tract infection in humans by novel HCoVs viruses named as HCoV-HKU1, HCoV-NL63 but predominant species is Middle East respiratory syndrome (MERS-CoV) across the world. HCoV-HKU1 sp. is associated with chronic pulmonary disease, while HCoV-NL63 causes upper and lower respiratory tract disease in both children and adults, but most recent one was MERS-CoV, which caused acute pneumonia and occasional renal failure. The novel coronavirus SARS-CoV-2 is a new strain that causes the Coronavirus Disease 2019 (COVID-19) as named by the World Health Organization. According to the recent world statistics report about the COVID-19 cases approx. 101,500 confirmed cases and 3,500 death cases appeared. And mostly, a case of infection with CoV was identified in Wuhan, China. Structurally viral genome constitutes of 2/3rd of replicase gene encoding ORFs regions and rest of the 1/3rd region of genome form the structural proteins. The aim of the study was to understand the viral genetic systems in order to facilitate the genetic manipulation of the viral genome and to know the fundamental mechanism during the viral replication, facilitating the development of antidotes against the virus.
Molecular Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: Hazardous and More Hazardous Strains Behind the Coronavirus Disease 2019 Pandemic and Their Targeting by Drugs and Vaccines
Frontiers in Cellular and Infection Microbiology, 2021
Within almost the last 2 years, the world has been shaken by the coronavirus disease 2019 (COVID-19) pandemic, which has affected the lives of all people. With nearly 4.92 million deaths by October 19, 2021, and serious health damages in millions of people, COVID-19 has been the most serious global challenge after the Second World War. Besides lost lives and long-term health problems, devastating impact on economics, education, and culture will probably leave a lasting impression on the future. Therefore, the actual extent of losses will become obvious only after years. Moreover, despite the availability of different vaccines and vaccination programs, it is still impossible to forecast what the next steps of the virus are or how near we are to the end of the pandemic. In this article, the route of molecular evolution of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thoroughly compiled, highlighting the changes that the virus has undergone during the...
Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments
Veterinary Quarterly, 2020
Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30 th , 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.
Review on Newly Identified Corona Virus and its Genomics Organization
SSR Institute of International Journal of Life Sciences
Human Coronaviruses (HCoV) exhibit positive single stranded RNA genome with enveloped nucleocapsid. Coronavirus belongs to the family Coronaviridae, originated from avian and mammalian species causes upper respiratory tract infection in humans by novel HCoVs viruses named as HCoV-HKU1, HCoV-NL63 but predominant species is Middle East respiratory syndrome (MERS-CoV) across the world. HCoV-HKU1 sp. is associated with chronic pulmonary disease, while HCoV-NL63 causes upper and lower respiratory tract disease in both children and adults, but most recent one was MERS-CoV, which caused acute pneumonia and occasional renal failure. The novel coronavirus SARS-CoV-2 is a new strain that causes the Coronavirus Disease 2019 (COVID-19) as named by the World Health Organization. According to the recent world statistics report about the COVID-19 cases approx. 101,500 confirmed cases and 3,500 death cases appeared. And mostly, a case of infection with CoV was identified in Wuhan, China. Structurally viral genome constitutes of 2/3rd of replicase gene encoding ORFs regions and rest of the 1/3rd region of genome form the structural proteins. The aim of the study was to understand the viral genetic systems in order to facilitate the genetic manipulation of the viral genome and to know the fundamental mechanism during the viral replication, facilitating the development of antidotes against the virus.
COVID-19 and SARS-CoV-2: Molecular Genetics Perspectives
Corona virus disease-19 (COVID-19) is a zoonotic viral disease caused by severe acute respiratory syndrome corona virus (SARS-CoV-2), which was first reported from Wuhan, Hubei province, in China in December 2019. The source of virus is believed to be from bats and the intermediate host is pangolins (ant eaters). The SARS-CoV-2 genome is fully sequenced and genome data are available now. Recent molecular studies on the three corona viruses-SARS-CoV, MERS-CoV(Middle East Respiratory Syndrome Corona virus), and SARS-CoV-2 can shed light on the mechanisms of COVID-19 infection, which could help the world to identify therapeutic target molecules, formulate control measures, and adopt appropriate preventive measures including development of vaccine(s).
A Comprehensive Overview of the Newly Emerged COVID-19 Pandemic: Features, Origin, Genomics, Epidemiology, Treatment, and Prevention
Biologics, 2021
The coronavirus disease 2019 (COVID-19), a life-threatening pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in massive destruction and is still continuously adding to its death toll. The advent of this global outbreak has not yet been confirmed; however, investigation for suitable prophylaxis against this lethal virus is being carried out by experts all around the globe. The SARS-CoV-2 belongs to the Coronaviridae superfamily, like the other previously occurring human coronavirus variants. To better understand a new virus variant, such as the SARS-CoV-2 delta variant, it is vital to investigate previous virus strains, including their genomic composition and functionality. Our study aimed at addressing the basic overview of the virus’ profile that may provide the scientific community with evidence-based insights into COVID-19. Therefore, this study accomplished a comprehensive literature review that includes the virus’ origin, classificat...
Understanding COVID-19, Genome, Epidemiology, Diagnosis, Treatment, and Vaccination
Journal of Bioscience and Applied Research
BioBacta
Pathogenetic profiling of COVID-19 and SARS-like viruses
Briefings in Bioinformatics, 2020
The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA-DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein-chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P...
Analysis of COVID-19 M Protein for Possible Clues Regarding Virion Stability, Longevity and Spreading
2020
The Severe Acute Respiratory Syndrome Coronavirus 2 or COVID-19 has been the cause of a global pandemic in 2020. With the numbers infected rising well above a 100,000 and confirmed deaths above 4000, it has become the paramount health concern for the global community at present. The COVID-19 genome has since been sequenced and its predicted proteome identified. In this study, we looked at the expected COVID-19 proteins and compare them to its close relative, the Severe Acute Respiratory Syndrome-Related Coronavirus. In particular we focussed on the M protein which is known to play a significant role in the virion structure of Coronaviruses. The rationale here was that since the major risk factor associated with COVID-19 was its ease of spread, we wished to focus on the viral structure and architecture to look for clues that may indicate structural stability, thus prolonging the time span for which it can survive free of a host. As a result of the study, we found some rather interest...
Managing the COVID-19 Pandemic: Research Strategies Based on the Evolutionary and Molecular Characteristics of Coronaviruses
SN Comprehensive Clinical Medicine, 2020
Coronavirus disease 2019 (COVID-19), an ongoing global health emergency, is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging in Wuhan, China, in December 2019, it spread widely across the world causing panic-worst ever economic depression is visibly predictable. Coronaviruses (CoVs) have emerged as a major public health concern having caused three zoonotic outbreaks; severe acute respiratory syndrome-CoV (SARS-CoV) in 2002-2003, Middle East respiratory syndrome-CoV (MERS-CoV) in 2012, and currently this devastating COVID-19. Research strategies focused on understanding the evolutionary origin, transmission, and molecular basis of SARS-CoV-2 and its pathogenesis need to be urgently formulated to manage the current and possible future coronaviral outbreaks. Current response to the COVID-19 outbreak has been largely limited to monitoring/containment. Although frantic global efforts for developing safe and effective prophylactic and therapeutic agents are on, no licensed antiviral treatment or vaccine exists till date. In this review, research strategies for coping with COVID-19 based on evolutionary and molecular aspects of coronaviruses have been proposed.
Related topics
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.