The COVID-19 Pandemic: Epidemiology, Molecular Biology and Therapy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global pandemic of Coronavirus Disease 2019 (COVID-19). More than 24.8 million global cases and 0.84 million deaths have been reported until the 31st August 2020. SARS-CoV-2 is like other human coronaviruses i.e. SARS and Middle East respiratory syndrome (MERS) but its transmission rate is much higher, biology is more complicated, and mechanism of action is still elusive. Certain individuals like elderly, males, people with type A blood group and persons with comorbidities (diabetes, hypertension, obesity, etc.) are susceptible to severe infection. One of the major concerns is that the asymptomatic individuals and persons in incubation period may also transmit the pathogen. Treatment of the affected individuals is symptomatic in the absence of antiviral drugs or vaccines. Collaborative clinical, epidemiological, molecular and immunological investigations are needed at warfooting across the globe to identify the evolutionary trajectories, mutational load, host immune response, therapeutics and vaccines against this pathogen. Pandemic has drastically affected the social life, economy, travel and transportation, educational systems, aviation, to name a few. However, it has a positive impact on the environment, wildlife, water bodies and forests. This warrants us to get ready to face aftermath scenario of this pandemic and rebuild the system. This by no means would be a simple task as it involves large scale resource mobilization, unprecedented development of sagging economy and infrastructures, rebooting the society, nations and the world after the default control-alt –delete mode of the pandemic.

The current pandemic disease (COVID-19) is caused by a highly infectious coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-Co- -2). It belongs to the family of Coronaviridae, subfamily Orthocoronaa-virinae, order Nidovirales. Coronaviruses (CoVs) are enveloped and spherical shaped pathogens with crown-like protrusions formed by S protein on the surface. The CoVs contain singlestranded positive-sense RNA with genome of 27-32 kb that encodes both structural and non-structural proteins. The Coronavirus genome encodes for at least 6 ORFs, among which two third parts include ORF 1a/1b, which encodes 16 non-structural proteins (nsp 1-16) that play a pivotal role in viral genome replication. The structural proteins are part of mature virion and include spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The S protein binds to the receptor (ACE2 or others) on the host cell and determines host tropism. Replication of CoVs is extremely complicated process and includes regulation at various stages including dependency on both the viral and host factors. The present chapter provides updated information about the morphology, genomic structure, properties and function of different proteins and their role in replication mechanism of SARS-CoV-2. The information about the proteins and their role in viral life cycle is likely to assist in the formulation of targeted therapeutic interventions and vaccines against this emerging respiratory pathogen.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global pandemic of Coronavirus disease 2019 (COVID-19). Limited information is available on evolutionary aspects of the structural proteins: spike (S), envelope (E), membrane (M) and nucleocapsid (N) of the virus. Therefore, we attempted detailed molecular and genetic characterization of SARS-CoV-2 structural protein genes using nucleotide composition, codon usage patterns, phylogenetic, entropy and selection pressure analyses. The RSCU patterns suggested codon biasness due to preference of U/A-ended over C/G-ended codons. Mutational pressure and natural selection influence the synonymous codon usage of structural protein genes in SARS-CoV-2. Phylogenetic analyses of different coronaviruses for all the four structural genes showed that all 2019-nCoV study sequences were clustered under the SARS-CoV-2 clade which was closest to bat coronaviruses. Additional phylogenetic analyses of SARS-CoV-2 structural protein genes showed discordance in the topology, suggesting different patterns of evolutionary relationships among these genes. Few non-synonymous amino acid mutations, low value of entropy and purifying selection suggested limited variations in the studied genes. However, these variations in the SARS-CoV-2 genome are likely to increase in near future since the virus will try to evade the host immune response to enhance its survival in humans. Thus, we evaluated the genetic diversity of the structural protein genes along with the genomic composition and codon usage patterns of SARS-CoV-2. Thus, present data on molecular characterization of structural protein genes is likely to augment the information about the evolution, biology and adaptation of SARS-CoV-2 in the human host.

The emergence of a global pandemic, COVID-19 is caused by the newly identified SARS-CoV-2. The current situation warrants us to understand the molecular basis of the evolution of this emerging pathogen. In this context, we conducted a comparative codon-based characterization of the viruses within the species Severe acute respiratory syndrome-related coronavirus (SARSr-CoV). We attempted phylogenetic analysis, and codon-based characterization by employing selection pressure and Shannon entropy analyses in the S2 subunit gene sequences of SARSCoV, Bat-SL-CoV and SARS-CoV-2. Further, the pattern of N-linked/O-linked glycosylation was analyzed within the SARS-CoV species. The phylogenetic analysis and pairwise distance calculations showed high similarities in the S2 subunit of SARSCoV- 2 with Bat-SL-CoVs. Our findings uncovered the low mean value of dN/dS, suggesting purifying selection, but certain codon positions were found to be under positive selection. The entropy analyses showed 71 codon positions having its high score. Three codon positions (160, 244 and 562) were identified to be positively selected with high entropy value suggesting that they are more prone to mutations. Further, the analysis revealed a conserved pattern in N-linked glycosylation though the discrepancies were found within the O-linked glycosylation pattern. Our findings may help in predicting the signature sequences based on the codon-based model of molecular evolution. Further, this approach may provide information on the evolutionary dynamics of this pathogen, facilitating much-desired control strategies against COVID-19.

Coronavirus Disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It started as an outbreak in Wuhan, China, at the end of 2019. But within a few months, it took the form of a deadly pandemic affecting millions of people in more than 216 countries. Transmission via a large number of asymptomatic cases and international travel played a pivotal role in the spread of infection to different geographical regions. In the present chapter, we have given the chronological details about the spread of the infection across the globe. The countries with the greatest international connectivity showed a large number of cases. Further, the countries that suspended international travelling and sealed their borders are the ones that have managed the spread impressively. Subsequently, we have summarized the emergence of human Coronaviruses (SARS, SARS-CoV-2 and MERS) in humans. We have also described the different modes of human to human transmission of SARS-CoV-2. However, the infectivity is undercounted as many patients with mild or no symptoms are not getting tested. The present chapter summarizes the origin, global epidemiology and modes of transmission of the infection. Comprehensive hospital and community-based surveillance and detailed interpretation of full genomes of SARS-CoV-2 need to be carried out across different geographical regions. This data will assist in the demarcation of mutation rates and resultant evolutionary trajectory of this emerging viral pathogen. Preventive measures like social distancing, wearing masks and good hygiene should be followed religiously to prevent the spread of the contagion.

Coronavirus disease 2019 (COVID-19) has spread to almost every part of the globe. Numerous risk factors have been identified for predisposition to severe infection. Age is reportedly an incredibly significant risk factor due to high fatality in the elderly population. Further, the infection is more predominant in males as compared to females, probably due to the difference in immunity, hormones, and some specific habits (smoking, drinking) that may influence the viral infection. Correlation of blood group with SARS-CoV-2 infection is also reported as individuals with type A blood group are probably more susceptible to the infection since it is native form. Type O blood group is an evolved form, and thus individuals with this group may be less susceptible to the infection. In addition, existing comorbid conditions like hypertension, diabetes, cardiovascular, endocrine, and chronic respiratory diseases are also associated with an increased risk of severe COVID-19. Obesity has also been reported to have a huge impact on the infection rate and post-infection results. There is also an apprehension of vertical transmission from pregnant females to foetus, but this aspect needs to be analysed in detail in future studies. This review summarizes the effects of different risk factors like age, gender, comorbidities, blood group and prenatal transmission on SARS-CoV-2 infection. The correlation of viral infection with genetic predisposition is another factor that can be explored in future studies. Detailed clinical studies involving large patient groups are required across the globe and on different ethnic populations to clearly define the role of risk factors to COVID-19.

The clinical symptoms of the Coronavirus Disease 2019 (COVID-19) may vary from asymptomatic to mild to severe to critical disease. The clinical symptoms include fever, body ache, severe weakness, cough, breathlessness, nausea/vomiting, diarrhoea, change in taste/smell, etc. The management of COVID-19 patients is in its evolutionary phase since the guidelines are being updated regularly due to the gradual addition of unique symptoms to the disease. A large number of asymptomatic cases, longer incubation periods, and high transmission rates are some of the concerns of the pandemic. The treatment is supportive in the absence of a specific therapeutic drug and a prophylactic vaccine. Numerous antipyretics, existing anti-viral drugs, antibiotics supplements, and other approaches are utilized for the management of COVID-19 patients. Though at early-stage (in the upper respiratory tract), the treatment of this infection is easier as compared to its advanced stage when the infection proceeds to the lower respiratory tract. Most of the severe cases may need hospitalization, regular monitoring, and oxygen supplementation. Patients with respiratory failure may need ventilator support. The SARS-CoV-2 mediated immune response has a significant impact on infection severity, which is represented as a cytokine storm and ultimately leads to acute respiratory distress syndrome (ARSD). The present chapter describes clinical manifestations and management of COVID-19 patients. Besides this, we have also discussed the host immune response and pathogenesis of the disease. Further comprehensive patient-based clinical studies will provide insight into the additional clinical manifestations, pathogenesis, and host immune response needed to clear the virus from the human body.

Coronavirus Disease 2019 (COVID-19) has spread rapidly across the world, leading to a pandemic. The diagnostic methods for COVID-19 are still in the evolutionary phase since scientists are continuously trying to implement the latest technologies to achieve this objective. The infection is difficult to diagnose in the early stage as patients can stay asymptomatic from 2 to 14 days or more. A rapid, sensitive, and specific reverse transcription real-time PCR (rRT-PCR) detects viral RNA and is used to detect early infections to prevent disease spread. Although the gold standard in diagnosis, this method cannot be implemented in remote areas because of the requirements of expensive setup and trained staff. Therefore, a relatively economical method known as loop-mediated isothermal amplification (LAMP), which also detects viral RNA, is designed for use at point-of-care and remote settings. The non-nucleic acid based rapid antigen detection method detects viral antigen on nasal/pharyngeal specimen and implies current viral infection. The serological diagnostic methods detect early serological markers (IgM/IgG) in the serum of patients after a week of infection. Antigen detection and serological diagnostic methods are rapid, specific, and sensitive, with the potential to screen a large number of people during a pandemic. Thus, the genome and antigen-based diagnostic assay can detect the virus in the early stages of infection, while serological methods can be used to diagnose infections at later stages. The combination of nucleic acid and non-nucleic acid laboratory detection methods can assist in a timely and accurate diagnosis of COVID-19 that will be a step towards better patient management and containment of the pandemic.

Research scientists across the globe are attempting to unearth the possible therapeutic agents against Coronavirus disease 2019 (COVID-19). The natural compounds from plant sources constitute a rich source of potential antiviral, antibacterial, antioxidant, anticancer, immune enhancer and other activities with minimal side effects. Approximately 25% of the European Medical Agency (EMA) or Food and Drug Administration (FDA) approved drugs are based on plant products highlighting their importance in the medical field. In recent years, in-silico methods have provided fast and cost-efficient approaches for designing potential inhibitors. Several virtual screening, molecular simulation, pharmacokinetics and druggability studies have been carried out to identify potential inhibitors against structural (spike, envelope, and membrane) and non-structural (Protease, RdRp, endoribonucleoase) proteins of SARS-CoV-2. In the present chapter, we have reviewed all such studies that recommended naturally occurring bioactive compounds (flavonoids, terpenes, curcuminoids, tannins, essential oil etc.) of plant origin as potential inhibitors of COVID-19. We have listed 100 such potential compounds and have analyzed significance of some of these (Myricitrin, Baicalin, Hesperidin, Theaflavin, Apigenin, Isothymol, Saikosaponin U, Curcumin, Tannin etc.) in detail based on computational studies. Furthermore, we have also studied several medicinal plants (Curcuma longa, Vitis vinifera, Glycyrrhiza glabra, Malus domestica, Azadirachta indica, Camellia sinensis and Nigella sativa). These plants are part of normal human diet and can also be considered as potential herbs with immune system enhancing effects. In addition, these phytoconstituents should be further analyzed in detail for toxicity, pharmacokinetics, antiviral and therapeutic potential in cell culture and animal models against SARS-CoV-2.

The current outbreak of the novel coronavirus disease known as COVID-19 caused by the newly identified coronavirus strain SARS-CoV-2 has become a prominent health problem worldwide. Therefore, there is an urgent requirement to uncover the specified preventive measures to control the spread of the disease. Different therapeutic approaches such as administration of corticosteroids, vitamins, trace elements, immune enhancers and convalescent plasma recovery can be good alternatives, but the current emergent situation demands specified treatment. The development of vaccines will require longer durations; therefore, deployment of existing drugs as a repurposing approach remains a great option to combat this pathogenic virus. WHO includes different categories of drug treatment options such as antivirals, antimalarial, antiparasitic, antifungal anti-inflammatory, immunosuppressants, inhibitors of kinase and protease monoclonal antibodies immunomodulators, ACE inhibitors and others. Antiviral drugs such as remdesivir, lopinavir/ritonavir, favipiravir, umifenovir and antimalarial drugs such as chloroquine/hydroxychloroquine, and several combinations of these drugs are being utilized in different clinical trials and have shown efficacy in the treatment of COVID-19. We have reviewed a general outline about these drugs in the present chapter along with the strategies that may be deployed in the identification of further antiviral agents. However, the side effects associated with their administration and their minimal and maximum dosage norms require special attention. Therefore, the safety and efficacy criteria for the available drugs need confirmation via further clinical trials.

The ongoing situation of COVID-19 pandemic entails us towards the development of a prophylactic vaccine as a public health priority. The emergence of SARS-CoV-2 in Wuhan, China during December 2019 marked the third introduction of a highly pathogenic Coronavirus into human population in the twenty-first century. Knowledge from the former vaccine candidates of SARS-CoV and MERS-CoV has unlocked the door for the developers to accelerate the global vaccine development pathway for ongoing COVID-19 pandemic, soon after the online publication of SARSCoV- 2 genomic sequence. The vaccine development pipeline for COVID-19 shows a promising result by utilizing various platforms (nucleic acid, viral vector, recombinant protein, live attenuated viruses, inactivated viruses and virus like particles) with different strategies. Surprisingly till now, we have about 190 vaccine candidates in the clinical and pre-clinical pipeline till 31st August 2020. Approximately, 39 of these vaccine candidates are impending into the human clinical trials after showing significant safety data in preclinical studies of which, 8 vaccine candidates are running in final phase3 stage. Three of them have got an emergency approval for limited or early use. At least 8 candidate vaccines have been developed from India, from which 2 of them have entered phase2 trials. Already existing tuberculosis vaccines are also being tested in clinical trials bridging the gap before a potential COVID-19 vaccine is developed. This chapter highlights the obstacles for implementation of vaccine development for SARS-CoV-2. One of the impediments is identification of high-risk population including frontline health care workers, elderly individuals and persons with pre-existing chronic diseases. We have also provided a comprehensive overview about the COVID-19 vaccine candidates that are in preclinical and clinical stages of development. Thus, fast track clinical trials of many candidates are implemented in different geographical regions promising a prophylactic vaccine against SARS-CoV-2.