Coronaviruses - Volume 2, Issue 8, 2021
Volume 2, Issue 8, 2021
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Boosting Innate Immunity During SARS-CoV-2 Clearance
Authors: Abhishesh K. Mehata, Deepa Dehari, Anuj Kumar Mehta and Alim MiyaCurrently, humanity is suffering from a highly contagious and infectious novel coronavirus disease. Due to the unavailability of any specifically approved therapy to eradicate this pathogenic virus, day by day, it is claiming more and more lives of humans. Observing the current scenario, human civilization seems to be in dangerous situation, and the development of a potential vaccine against this invisible enemy may take some more time. It was observed that the individual immune system plays an important role in the fight against the novel coronavirus. Additionally, the innate immune system of the host acts as the first line of defense against invading pathogenic viruses. The host innate immune cells can detect and detoxify the evading viruses. Thus, boosting the innate immune response via targeting activator or inhibitory immune check points pathways for enhancing T-cell immune response may potentially help the patients to fight against this deadly virus. The aim of this editorial is to discuss in brief about the pathogenesis of COVID-19, the role of innate immunity and autophagy during viral clearance.
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Impact of Metaheuristic Techniques in Pandemic of COVID-19
Authors: Vijay Kumar, Dilbag Singh and Manjit KaurThe early detection and diagnosis of novel coronavirus disease 2019 (COVID-19) are required to cure the disease. Metaheuristic techniques can be used to develop an automated tool for detecting the symptoms of an infected person and provide appropriate precautionary measures. The metaheuristic-based software can be designed to analyze the radiographic patterns of infected individuals and determine the severity of COVID-19 infection. The genome structure of coronavirus can be easily understood through metaheuristic techniques. Based on the genome structure, an effective drug combination can be explored by using metaheuristics for the treatment of COVID-19.
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Design and Development of Smart and Safe Helmet for Inhibiting COVID-19 Virus Infection: A Simple Idea for Solving the Big Crisis
By C ManjunathaThe coronavirus disease 2019 (COVID-19) has recently spread worldwide due to the SARS-CoV-2 virus and has been declared a pandemic. A possible solution to prevent or restrict the spread of the COVID-19 pandemic is proposed in this article. Uncontrolled spread of the virus through breathing is a major concern. It is ideal if the entry of the virus inside the human body is restricted, as prevention is better than cure. Use of a “Smart-HELMET” that allows uncontaminated air (virus/bacteria/microbes-free) to breathe is proposed. The design of the Smart-HELMET, its working mechanism, the chemistry and biology of the virus-cell interaction inside a human body are discussed in detail. The proposed ‘Smart-HELMET’ prevents the spread of any respiratory illness through breathing. This is the need of the hour until a medicine/vaccine is made available in in vivo condition.
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A Perspective on the Impact of COVID-19 Pandemic on Basic Science Research and its Future Implications
COVID-19 has emerged as a devastating pandemic of the century that the current generations have ever experienced. The COVID-19 pandemic has infected more than 12 million people around the globe, and 0.5 million people have succumbed to death. Due to the lack of effective vaccines against the COVID-19, several nations throughout the globe have imposed a lock-down as a preventive measure to lower the spread of COVID-19 infection. As a result of lock-down, most of the universities and research institutes have witnessed a long pause in basic science research ever. Much has been discussed about the long-term impact of COVID-19 on the economy, tourism, public health, small and large-scale businesses of several kinds. However, the long-term effects of the shut-down of these research labs and their impact on basic science research has not been much focused. Herein, we provide a perspective that portrays a common problem of all the basic science researchers throughout the globe and its long-term consequences.
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SARS-CoV-2: Evaluation and Evolution
The emerging new COVID 2019 pandemic, which started in 2019 in China (Wuhan) and is caused by SARS-CoV-2, raises critical concerns due to high morbidity and mortality. As many patients are infected and the numbers still increase, this may suggest that there are different variants of the virus and some of them are more pathogenic. Besides, the virus is suspected to have various evolutionary pathways since SARS-CoV-2 belongs to the RNA viruses’ family, which is characterized by a high mutation rate. Additionally, it is crucial to understand the life cycle of the virus to be able to urge antiviral studies. Genotyping studies about viruses are also important in order to understand the transmission and evolution of the virus. The genome of SARS-CoV-2 has a furin-like cleavage site in its S protein that may affect its pathogenicity. It was found that insertions and deletions in S protein have an impact on the transmission and fusion of the virus. The single nucleotide polymorphisms (SNP) genotypes are used to track the relationship of virus isolates. Sequence alignment revealed the presence of hundreds of inter-host mutations during person-to-person transmission. Furthermore, genetic recombination provided a second mechanism for virus evolution. In this review, we highlight the life cycle of the virus and methods of virus evolution caused by mutations or recombination of viral genomes
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COVID-19 Pandemic: Current Scenario, Challenges and Future Perspectives
Authors: Ovais Zargar, Rohina Bashir, Mohammad A. Zargar and Rabia HamidBackground: The new public health emergency of COVID-19 caused by a novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which originated in Wuhan, Hubei province, China in December 2019, evolved into a pandemic in no time and is still in progression. The novel virus mainly targets the lower respiratory system, leading to viral pneumonia, with other associated complications of multi organ failure. Discussion: The bats, in particular Rhinolophus affinis, is a natural host of SARS-CoV-2 and the virus is considered to have spread to humans through yet controversial intermediate host pangolins. The incubation period ranges from 2-14 days and mode of person-to-person transmission is primarily via the direct contact with the infected person or through the droplets generated by the infected person during coughing or sneezing. The initiation of the infection process by SARS-CoV-2 virus is the invasion of lung type II alveolar cells via a receptor protein called angiotensin-converting enzyme 2 (ACE2) present on the cell membrane with glycosylated spike (S) viral protein that mediates host cell invasion. The main diagnostic tools employed are molecular methods based on nucleic acid detection engaging real-time quantitative polymerase chain reaction (RT-qPCR) and a new immunoassays based on antibodies IgM/IgG. Conclusion: Due to the lack of specific clinically approved anticovid-19 drugs or vaccines that could be used for its prevention or treatment, the current management approach is essentially supportive and symptomatic. The precautionary measures like, social distancing, cleaning hands with soap or sanitizers, using disinfectant solutions to decontaminate the surfaces of things and proper ventilation, wearing masks and other protective gears to curb transmission. The knowledge regarding COVID-19 therapies is still evolving and collaborative efforts are being put in to discover definitive therapies on different themes in the form of vaccines, repurposing drugs, RNA interference, docking studies, etc.
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Remdesivir (GS-5734) for COVID-19 Treatment: Past and Recent Updates
Authors: Santhosh Arul and Haripriya DayalanBackground: SARS-CoV-2 is a pandemic now, and several measures have been taken by countries to prevent, control, and treat the disease. WHO has been working meticulously and has been providing up to date information and statistics on incidences and death. Several broad- -spectrum anti-viral drugs are available and have been used in the past to fight against the viral outbreak. Recently remdesivir, an experimental prodrug from Gilead Sciences, has been found to be a potential drug to be used as a therapy to treat COVID-19. Objective: Here, we have reviewed several previous findings from the literature and present an up to date information on remdesivir. Result: Remdesivir was initially invented for use against Ebola virus treatment and has proved effective against different strains of Ebola, Nipah, and other strains of coronaviruses. Clinical trials with remdesivir for COVID-19 patients have begun, and several off label use of remdesivir have been reported recently. Currently, the drug seems to have an effect against the SARS-CoV-2 virus, with side effects among a few patients. Although the results are not conclusive, they are partly promising. This review provides past and recent updates on the use of remdesivir. Conclusion: From the review, we conclude that the drug remdesivir is known to exhibit its mechanism of action by terminating the RNA synthesis, and it is a potential drug against the novel coronavirus.
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A Review on Coronavirus Disease- A Future Challenge for Mankind (Focusing on Indian Situation)
Authors: Ekta R Raut and Archana R RautToday, the entire world is facing a big medical calamity called COVID-19. It is caused by a member of the β group of coronaviruses named SARS-CoV-2. This virus spreads from person to person through droplets generated during coughing and sneezing from the human body. This outbreak was initially observed in Wuhan, China, and now it has spread from country to country. As per the data collected from Worldometer, about 210 countries and territories were affected by this disease. Globally, as of 25th August 2020, there have been 23,518,343 confirmed cases of COVID-19, including 810,492 deaths. The most affected countries include USA, Brazil, India, Russia and South Africa, having more than 6, 00,000 infected people as of 25th August 2020. This outbreak of coronavirus is increasing worldwide, and this situation not only prepares mankind for fighting today's challenge but is also preparing for such type of future outbreaks. This paper highlights the symptoms, preventive measures and future challenges of COVID-19 based on the data referred from the World Health Organization (WHO).
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Stroke and COVID-19 Pandemic: The Dilemma
Background: While the COVID-19 pandemic affected more than thirty million people world-wide, still the true link between COVID-19 and the incidence of stroke remains to be elucidated. Methods: Herein, we briefly discuss virology of COVID-19 and approaches for diagnosis and treatment of COVID-19 patients, as well as the mechanisms that link stroke and COVID-19. Results: Many pathophysiologic and immunologic mechanisms have been implicated in stroke occurring among patients with COVID-19. COVID-19 pandemic has, in different ways, negative impacts on the care of stroke patients world-wide, and still, neurologists have to face many challenges to improve the care of stroke patients during such crisis. Conclusion: Although the control of the COVID-19 is of crucial importance, at the same time, the management of stroke must not be neglected. Therefore, preserving care for critical conditions such as stroke, and providing strategies to ensure this continues, have a priority even during the crisis. Till vaccine is available for COVID-19, strategies for rapid diagnosis and those for treating patients with that disease are evolving. Further studies are warranted.
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Remdesivir, A Potential Drug for COVID-19 Treatment: A New Hope
Authors: Kuldeep Singh, Dilpreet Singh and Karan RazdanObjective: Coronavirus Disease-2019 (COVID-19) is a pandemic outbreak in the world and is the leading cause of Severe Acute Respiratory Syndrome (SARS). Methods: Currently, many drugs/therapies have been tested for COVID-19, which responded sub- -optimally to the patients. Remdesivir is an RNA polymerase inhibitor that found promising results in ongoing clinical trials and shows a faster recovery rate in COVID-19 patients. Currently, USFDA approves for emergent use of this drug in severe COVID-19 patients. Results: In this review, we discussed a brief overview of biopharmaceutical and pharmacological aspects of Remdesivir. Moreover, the ongoing regulatory status of Remdesivir by official bodies has also been described.
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2019 Novel Coronavirus: A Review on Epidemiology, Pathophysiology, Diagnosis and Current Clinical Trials in Vaccine Development
Coronavirus disease-2019, a viral disease caused by the novel severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), was identified by the Centre for Disease Control (CDC), China, on January 7, 2020. This mysterious respiratory epidemic occurred in Wuhan, China, in late December 2019. A month after its outbreak in China, the World Health Organization (WHO) declared it as a public health emergency of international concern (PHEIC) due to its severity and high transmission potential throughout the world, leading many nations to implement multiple lockdown sessions and strict social distancing measures. As of September 21, 2020, 30,675,675 active cases and 954,417 deaths had been reported worldwide. Intensive research is being carried out across the globe to identify precise diagnostic techniques and develop novel, effective vaccines against the virus. Herein, we elaborate on details of epidemiology, genetics, pathophysiology, diagnosis, prevention, and vaccine trials related to this pandemic.
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Management of COVID-19 very Elderly Patients in Nursing Homes and Long-Term Care Facilities: Description of a New Model and Experience in a Medicalized Nursing Home
Introduction: COVID-19 has been a challenge for healthcare, mainly in elderly patients in Nursing Homes (NHs) and Long-Term Care Facilities (LTCFs). We present a pioneering novel experience in addressing healthcare of elderly patients with COVID-19 in these facilities by a reconversion of a NH in a medicalized NH. Methods: All patients admitted to the center were included, recording clinical and epidemiological variables. We conducted a descriptive analysis and a multivariate analysis to identify variables linked to mortality and persistence of positive PCR test. Results: 84 patients were included (40% men), women presented more symptomatology. We found a positive correlation between the duration of symptoms and the days required to obtain a negative PCR test (r=0.512, P<0.001). We also found an independent and significant association between asthenia (OR=2.58; IC95% 1.22-5.46) and mutism (OR=5.21; IC95% 1.58-17.15) and a longer time to achieve a negative PCR test. All patients, except contraindication, were treated with hydroxychloroquine and azithromycin, which was the recommended treatment during the period of the study. The early start of corticoid treatment (within the first 72 hours since the start of symptoms) was linked to a lower mortality in patients with moderate-severe symptoms. Mortality was lower than expected (which was higher than 20% in that period and group of age), reaching 14%, the main factors linked to mortality were the presence of mutism (OR=19; IC95% 3.4-108; P=0.001) and dyspnea (OR=12; IC95% 1.3-111; P=0.029). Conclusions: An alternative system was presented for the care of these patients through the reconversion of a basic NH in a medicalized one, which showed a significant reduction in the expected mortality.
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Docking Studies with Multiple Molecular Targets Associated with SARSCoV- 2 for Drug Repurposing
Authors: Shiwani Rana, Meghali Panwar and Kalyan S. GhoshBackground: The current pandemic outbreak of COVID-19 due to viral infections by SARS-CoV-2 has now become associated with severe commotion on global healthcare and the economy. Objective: In this extreme situation, when vaccine or effective new drugs against COVID-19 are still not available, the only quick and feasible therapeutic alternative would be the drug repurposing approach. Methods: In the present work, in silico screening of some anti-viral and antiprotozoal drugs was performed based on docking using Autodock. Results: Two known anti-viral drugs, sorivudine and noricumazole B, are predicted to bind to the active site of the viral proteases, namely cysteine-like protease or 3CL protease (3CLpro) and papain- like protease (PLpro), respectively, with a highly favorable free energy of binding. Further, the promising molecules were subjected for checking their activity on other molecular targets in SARS-CoV-2 like spike protein S1, RNA dependent RNA polymerase (RdRp), and angiotensin converting enzyme 2 (ACE2) receptor. But the compounds were found non-effective on the rest of the molecular targets. Conclusion: Sorivudine alone or a combination of sorivudine and noricumazole B may be administered to impede viral replication, though the predicted drug likeliness of noricumazole B is not much satisfactory. These observations are solely based on the results from blind docking with protein molecules and need to be further corroborated with experimental results.
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In-silico Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors against Main Protease of SARSCoV- 2
Authors: Ravi S Patel, Akash G Vanzara, Nimisha R Patel, Ajit M Vasava, Sachin M Patil and Kishore S RajputBackground: Emergence of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Methods: High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum triplex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and dihydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Results: A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion: Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.
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In Silico Identification of Potential Inhibitors of SARS-CoV-2 Papain-like Protease From Natural Sources: A Natural Weapon to Fight COVID-19
Authors: Bimal Debnath, Pradip Debnath, Rajat Ghosh and Sudhan DebnathBackground: The rapid spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) globally has created unprecedented health care and economic crisis. The ever-increasing death toll highlights an urgent need for the development of specific antiviral to combat Novel Coronavirus Disease 2019 (COVID-19). Objective: In the present study, we aimed to identify potential SARS-CoV-2 papain-like protease inhibitors from regularly used spices. Methods: A structure-based virtual screening (VS) of our in-house databank of 1152 compounds was employed to identify small molecule inhibitors of SARS-CoV-2 papain-like protease (PLpro), which are important protease for virus replication. The databank was built of the compounds from ten spices and two medicinal plants. Results: The top three potential hits that resulted from VS were myricetin (1) available in Alium cepa and Mentha piperita; α-hydroxyhydrocaffeic acid (2) available in M. Piperita; and luteolin (3) available in M. Piperita, Curcuma longa, A. cepa, and Trigonella foenum-graecum, which showed fair binding affinity to PLpro of SARS-CoV-2 compared to known SARS-CoV PLpro inhibitors. The predicted Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the selected hits showed that all are drug-like. The compounds bind to biologically critical regions of the target protein, indicating their potential to inhibit the functionality of this component. Conclusion: There are only a few reports available in the literature on the in-silico identification of PLpro inhibitors and most of them used homology modeling of protein. Here, we used the recently uploaded X-ray crystal structure of PLpro (PDB ID: 6WX4) with a well-defined active site. Our computational approach has resulted in the identification of effective inhibitors of SARS-CoV-2PLpro. The reported edible spices may be useful against COVID-19 as a home remedy after an in- -vitro study.
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