&lt;strong&gt;Pathogenesis, Diagnosis and Possible Therapeutic Options for COVID-19&lt;/strong&gt;

Ullah, Md. Asad; Araf, Yusha; Moin, Abu Tayab; Reshad, Riyan Al Islam; Rahman, Md. Hasanur

doi:10.20944/preprints202004.0372.v1

Cited by 8 publications

(9 citation statements)

References 62 publications

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“…Till date, only four genera of these viruses have been identi ed, namely α, β, γ and δ. Among the human coronaviruses, HCoV-229E and NL63 fall under α category and MERS-CoV, SARS-CoV, HCoV-OC43 and HCoV-HKU1 fall under β category [10][11][12][13]. Scientists predict 14 functional ORFs within the SARS-CoV genome, which include the replicase and protease genes, the spike (S), envelope (E), membrane (M), and nucleocapsid (N) genes (order of appearance: 5′ to 3′) [10,14].…”

Section: Introductionmentioning

confidence: 99%

In silico analysis of RNA-dependent RNA polymerase of the SARS-CoV-2 and potentiality of the pre-existing drugs

Mukhoty

Ghosh

et al. 2020

Preprint

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Background: The alarming increase in the number of SARS-CoV-2 cases worldwide, urgently demands far-reaching effective strategies to win the battle against emerging as well as re-emerging diseases. Many research laboratories are conducting clinical trials with different drugs, among which some became quite interestingly effective against this pandemic. Our aim is to investigate the potentiality of the pre-existing drugs and get a clear understanding of their effects on RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2. Methods: Multiple sequence alignment (MSA) alogwith molecular phylogeny analysis were performed using homologous sequences to identify the mutations within RdRp and evolutionary relationship. Based on the published literatures, we have chosen eight drug molecules like Ribavirin, Tenofovir, Sofosbuvir, IDX-184, YAK, Setrobuvir, Remdesivir and Galidesivir. Series of molecular docking studies between template RNA and RdRp of SARS-CoV-2 has been performed in absence or presence of those drugs and cofactors nsp7 and nsp8.Results: From MSA 13 exclusive mutations identified within RdRp of SARS-CoV-2 and phylogeny reveals its close relation with Bat coronavirus RaTG13. The interaction affinities and interacting residues as obtained from systematic molecular docking study led to a conclusion that the chosen drugs can prove to be effective against this pandemic partially. Conclusion: Therefore, designing of inhibitors which will specifically act against nsp12 and lower the binding affinity of nsp12 towards RNA template is necessary. In this article we additionally focus on the nsp7-8 hexadecameric complex and had suggested a list of amino acid residues of nsp12 and nsp7-8 complex to develop far-reaching effective drugs.

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Section: Introductionmentioning

confidence: 99%

In silico analysis of RNA-dependent RNA polymerase of the SARS-CoV-2 and potentiality of the pre-existing drugs

Mukhoty

Ghosh

et al. 2020

Preprint

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“…This disease was originated in Wuhan City of Hubei Province of China in December, 2019. But now, its spread is abruptly accelerated on a worldwide scale from its origin (Ullah et al, 2020a, Islam et al, 2020. Coronaviruses (CoVs) are a group of immensely diversified RNA viruses with some general features i.e.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, an effective subunit vaccine was focused to develop against various isolates of SARS-CoV-2 from different countries across the world, utilizing the immunoinformatics approach. In immunoinformatics, the novel antigens of a pathogen or virus are identified by dissecting its genomic data and then different tools of in silico biology and bioinformatics are used for vaccine designing and development by analyzing its genome (Chong & Khan, 2019;Rappuoli, 2000;Sarkar et al, 2020a). In our study, a blue print of epitope-based vaccine was designed which might produce substantial immune response towards SARS-CoV-2, isolated from different countries around the world, targeting the spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein of the virus.…”

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confidence: 99%

Engineering Novel Epitope-Based Subunit Vaccine against SARS-CoV-2 by Exploring the Immunoinformatics Approach

Sarkar¹,

Ullah²,

Araf³

et al. 2020

Preprint

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As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

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“…The pandemic of COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and presents a challenge in regard to identifying effective drugs for prevention and treatment. Up to the time of writing this manuscript, there were no medications approved by the U.S. Food and Drug Administration (FDA) to treat COVID-19 7 . However, the FDA recently created a new emergency program, the Coronavirus Treatment Acceleration Program (CTAP), aimed at speeding up research for the development of COVID-19 treatments 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial

Abbas

Al‐Jumaili

Nassir

et al. 2020

Preprint

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The goal of this study was to assess the clinical effectiveness and safety profile of the COVID-19 treatment protocol (containing both hydroxychloroquine (HCQ) and azithromycin) in an Iraqi specialized hospital. Methods: This prospective study used a pre-and post-intervention design without a comparison group. The intervention was routine Ministry of Health (MOH) approved management of COVID-19 for all patients. The study was conducted in a public healthcare setting in Baghdad, Iraq from March 1st to May 25, 2020. The study outcome measures included the changes in clinical and biochemical parameters during the hospitalization period. Paired t-test and Chi-square test were used to compare the measures of vital signs, lab tests and symptoms before and after treatment. Results: The study included 161 patients who were admitted with positive RT-PCR and clinical symptoms of COVID-19. In terms of severity, 53 (32.9%) patients had mild condition, 47 (29.2%) had moderate condition, 35 (21.7%) had severe condition, and 26 (16.1%) had critical condition. Most patients (84.5%) recovered and were discharged without symptoms after testing negative with RT-PCR, while 11 (6.8%) patients died during the study period. The signs and symptoms of COVID-19 were reduced significantly in response to therapy regimen containing HCQ and azithromycin. The most common reported side effects were stomach pain, hypoglycemia, dizziness, itching, skin rash, QT prolongation, arrhythmia, and conjunctivitis. Conclusions: This natural trial showed that COVID-19 regimen containing both HCQ and azithromycin can be helpful to promote recovery of most patients and reduced their signs and symptoms significantly. It also shows some manageable side effects mostly those related to heart rhythm. In the absence of FDA-approved medications to treat COVID-19, the repurposing of HCQ and azithromycin to control the disease signs and symptoms can be useful.

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<strong>Pathogenesis, Diagnosis and Possible Therapeutic Options for COVID-19</strong>

Cited by 8 publications

References 62 publications

In silico analysis of RNA-dependent RNA polymerase of the SARS-CoV-2 and potentiality of the pre-existing drugs

In silico analysis of RNA-dependent RNA polymerase of the SARS-CoV-2 and potentiality of the pre-existing drugs

Engineering Novel Epitope-Based Subunit Vaccine against SARS-CoV-2 by Exploring the Immunoinformatics Approach

Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial

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