Pharmaceutical Sciences
Volume:27 Issue: 3, Nov 2021

Several studies have suggested the positive impact of vitamin D on patients infected with SARS-CoV-2. This systematic review aims to evaluate the effects of vitamin D supplementation on clinical outcomes and mortality rate of COVID-19 patients.

A comprehensive search was conducted through the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library without time and language limitation, until December 16, 2020. The results were screened, and the outcomes of interest were extracted. Using the Joanna Briggs Institute (JBI) Critical Appraisal Tools, the remaining results were appraised critically. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA) software version 2.0.

Of the 2311 results, four studies and 259 patients were enrolled, including 139 patients in vitamin D intervention groups. The pooled analysis of three studies, reporting the patients’ survival and mortality rate, showed a significantly lower mortality rate among the intervention groups compared with the control groups (OR=0.264, 95% CI=0.099–0.708, p-value=0.008). Two of the studies reported the clinical outcomes based on the World Health Organization’s Ordinal Scale for Clinical Improvement (OSCI) score for COVID-19, where both of them showed a significant decrease in OSCI score in the vitamin D intervention groups. One study reported a lower rate of intensive care unit (ICU) admission, and one study reported a significant decrease in serum levels of Fibrinogen.

Prescribing vitamin D supplementation to patients with COVID-19 infection seems to decrease the mortality rate, the severity of the disease, and serum levels of the inflammatory markers. Further studies are needed to determine the ideal type, dosage, and duration of supplementation.

The effective responses of both innate and adaptive immunity are crucial in combating novel coronavirus-2 infection. An excessive response may lead to cytokine storm, which is a challenging problem in therapeutic strategies.

A systematic review was carried out by searching Ovid MEDLINE, PubMed, Google Scholar, and Cochrane library databases from inception, for anti-inflammatory and immunomodulatory drugs against coronavirus disease 2019 (COVID-19).

The results of the effectiveness of Hydroxychloroquine are just like a sinusoidal diagram and in a state of ambiguity. Thalidomide was effective in some cases but has not yet been proven. Low-dose Corticosteroids may be effective in the early stages of the illness as a bridge. There is no evidence of benefits or adverse outcomes for the use of non-steroidal anti-inflammatory drugs and Cyclosporine-A. In some critically ill patients, Interleukin-6 (IL-6) and IL-1 blockers and to some extent, Tumor-Necrosis-Factor-α and Janus-Kinase inhibitors are useful. Finally, high-dose intravenous immunoglobulin reversed the deterioration of patients in most trials.

One strategy behind the treatments for COVID-19 is based on breaking the cytokine storm. Although avoiding the suppression of anti-viral immunity is crucial by choosing the weaker and more selective anti-inflammatories, some strategies are kept for hyper-inflammatory situations. Scheduling of treatment is also important. Although low-dose steroids may be effective in the early stages of the illness, “Tocilizumab” is more effective in severe situations, when the IL-6 level is high and other drugs are ineffective. Therefore, consideration should be given to each patient separately

The coronavirus disease 2019 (COVID-19) outbreak has caused a public health crisis worldwide. However, data regarding the protective factors of the disease is limited. Consequently, preventive health measures that can decrease the risk of infection, progression, and severity are dreadfully required. It is well-documented that people with immunodeficiency, such as the elderly, people who already have comorbidities (e.g., diabetes mellitus, hypertension, respiratory and cardiovascular disorders), and underrepresented minorities, are placed in a group with a higher risk of getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A diet rich in vitamins, minerals, and antioxidants plays an essential role in strengthening the immune system and fighting against invading pathogens. The present comprehensive review has discussed published literature regarding the potential role of vitamins in strengthening the immune system and managing viral infections, particularly SARS-CoV-2 infection. Although there are controversial data regarding the plasma level of vitamin D and the severity of the disease, according to the limited evidence, vitamin D may lower the mortality rate. Moreover, vitamin C could reduce the development of inflammatory response; however, the results of ongoing clinical trials are required to confirm these primary findings.

A series of cases of pneumonia occurred in China in late 2019. For this type of coronavirus, the World Health Organization (WHO) formally identified the condition as a coronavirus disease 2019 (COVID-19). They announced that this disease is the recent main concern of health problems in the world. Transfer of this novel coronavirus (nCoV) from human to human exists predominantly among family members, who have close contact with each other. This review article is provided based on the recent findings of COVID-19, which were retrieved by searching PubMed, Google Scholar, Scopus, and Web of Science until December 2020. Here, we highlighted the coronaviruses types, COVID-19 symptoms, epidemiology of the disease, transmission ways, and nCoV related pneumonia pathogenesis and continue with characteristic features and treatment methods. While no approved treatments are available for this type of infection therapy but several drugs may have potential benefits. It seems that identifying the detailed characteristics of the novel coronavirus disease offers the foundation for further research into the production of effective anti-COVID-19 drugs and vaccines.

There are successful reports of the concomitant management of herpes infection and coronavirus disease 2019 (COVID-19), using both acyclovir (ACV) and COVID-19 treatment regimens. Furthermore, ACV has been proposed to effectively treat COVID-19, through various mechanisms, such as inhibition of viral proteases, multiple viral gene expressions, and RNA- dependent RNA polymerase (RdRP). Therefore, this study aimed to review the reported cases of patients with concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions.

A search was done to find the relevant articles, published between December 2019 and December 2020, with no language limitations, in the PubMed database, using the Medical Subject Headings (MeSH) terms related to herpes simplex virus or herpes zoster (namely, shingles) combined with COVID-19. Accordingly, the reports of the concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions were included.

Out of 90 articles, 11 records reporting the cases of herpes infection and concurrent laboratory-confirmed COVID-19, receiving antiherpetic therapies, were reviewed. There were 28 patients (age range of 7-82 years) with laboratory-confirmed COVID-19, concomitant with reactivation of herpes infection, receiving antiviral drugs alongside candidate COVID-19 treatment regimens, but no mortality. The mean (standard deviation [range]) age of these 28 patients during treatment was 56.4 (18.6 [7-82]) years, and the majority were male (n=18, 64.3%). A total number of 20 patients had also received ACV and eight cases had been administered with other two antiviral compounds, including seven cases with valacyclovir, and one case with famciclovir, with no mortality.

The potential use of ACV, as an add-on therapy, along with candidate COVID-19 treatment regimens was proposed in this study. However, further clinical trials are recommended to test this hypothetical adjuvant therapy.

COVID-19 is the latest human crisis to hit most parts of the world since its emergence in China. High prevalence, rapid transmission, and high mortality rates make it necessary to find an effective therapy immediately. Repurposing the available drugs with well-known side effects is proven to be a viable and efficient way to treat this disease. The study purposed to evaluate the therapeutic effect of direct-acting anti-hepatitis C drugs in COVID-19 by reviewing the articles in PubMed, Scopus, Google Scholar, and Embase databases. Some studies mentioned a high similarity between the hepatitis C virus and coronavirus in genome structure and molecular properties. Accordingly, anti-HCV drugs can have a good preventive effect on the actions of SARS-CoV-2 structural and nonstructural proteins. Molecular docking results have shown that anti-hepatitis C drugs such as sofosbuvir, daclatasvir, simeprevir, and elbasvir tend to form various stable bonds with the active sites of essential SARS-CoV-2 proteins. So these drugs can disrupt viral replication and its pathogenesis. Among anti-HCV drugs, sofosbuvir and daclatasvir work efficiently in molecular and human studies. In some human studies, the addition of sofosbuvir/daclatasvir to the therapy of COVID-19 resulted in a shorter duration of hospitalization and higher recovery rates. However, the confirmation of these medications needs more detailed clinical studies in large patient populations.

The coronavirus 2019 disease (COVID-19) is an ongoing outbreak of respiratory disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus can invade various tissues and organs, causing multiple organ dysfunctions. Critically ill COVID-19 patients may develop acute respiratory distress syndrome and pneumonia, which are the major causes of hypoxemic respiratory failure and death due to SARS-CoV-2 infection. Thus, ventilation support (invasive or noninvasive), has become a common practice in respiratory treatment of COVID-19 patients. Patients receiving mechanical ventilation usually require sedation to alleviate anxiety, pain and discomfort. On the other hand, current clinical reports have indicated that a significant number of COVID-19 patients require prolonged intensive care unit (ICU) care and ventilation, which increases the risk of delirium. Thus, selection of appropriate sedative medications during this period is of utmost importance. Dexmedetomidine (DEX) is a sedative, anxiolytic and analgesic agent that acts through the α2-adrenoceptor. Its sedative property is notable due to the lack of respiratory depression. In addition, its cytoprotective, immunoregulatory and anti-inflammatory properties have been well established in preclinical settings. Based on these features, a number of recent studies have proposed DEX as a beneficial sedative agent that simultaneously mitigates the excessive inflammation and protects vital body organs in patients with severe COVID-19. In current brief review, we aimed to discuss the therapeutic benefits of DEX in managing different indications of COVID-19.

The current outbreak of Coronavirus Disease 2019 (SARS-CoV-2) led to public health emergencies all over the world and made it a global concern. Also, the lack of an effective treatment to combat this virus is another concern that has appeared. Today, increasing knowledge of biological structures like increasing computer power brings about a chance to use computational methods efficiently in different phases of drug discovery and development for helping solve this new global problem.

In this study, 3D pharmacophores were generated based on thirty-one structures with functional affinity inhibition (antiviral drugs used for SARS and MERS) with IC50<250 μM from the literature data. A 3D-QSAR model has been developed and validated to be utilized in virtual screening.

The best pharmacophore models have been utilized as 3D queries for virtual screening to gain promising inhibitors from a data set of thousands of natural compounds retrieved from PubChem. The hit compounds were subsequently used for molecular docking studies to investigate their affinity to the 3D structure of the SARS-CoV-2 receptors. The ADMET properties calculate for the hits with high binding affinity.

The study outcomes can help understand the molecular characteristics and mechanisms of the binding of hit compounds to SARS-CoV-2 receptors and promising identification inhibitors that are likely to be evolved into drugs

Drug repurposing is the fastest effective method to provide treatment for coronavirus disease (COVID-19). Drugs that targeting a closely related virus with similar genetic material such as hepatitis C virus (HCV) and more specifically targeting a similar viral protease would be an excellent choice.

In this study, we carried out a virtual screening for fifteen anti HCV drugs against COVID-19 main protease using computational molecular docking techniques. Moreover, Velpatasvir (4) and Sofosbuvir (13) drugs were further evaluated through molecular dynamics simulations followed by calculating the binding free energy using the molecular mechanics generalised born/solvent accessibility (MM-GBSA) approach.

The binding affinity descending order was N3 natural inhibitor (1), Velpatasvir (4), Sofosbuvir (13), Ombitasvir (3), Glecaprevir (2), Asunaprevir (8), Paritaprevir (10), Grazoprevir (11), Elbasvir (6), Ledipasvir (5), Daclatasvir (7), Pibrentasvir (9), Simeprevir (12), Dasabuvir (14), Taribavirin (16) and finally Ribavirin (15). Molecular dynamics simulation reveals that Sofosbuvir (13) has exciting properties and it was stable within the active site and also showed good MM-GBSA compared to the natural inhibitor N3.

Our results could be auspicious for fast repurposing of the examined drugs either alone or in combinations with each other for the treatment of the COVID-19. Furthermore, this work provides a clear spot on the structure-activity relationship (SAR) for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease and helps the design and synthesis of new drugs in the future targeting it as well.

A significant worry for global public health is the international spread of the coronavirus disease-19 triggered through the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, an attempt was performed to qualitative and quantitative analysis of a series of compounds against SARS-CoV-2 main protease (M<[pro]) by in silico studies.

About one hundred anti-viral compounds were collected from DrugBank database. In the second stage, molecular docking simulation was carried out to identify interactions of the molecules with the key residues in the M<[pro] active site. Finally, the molecular dynamics simulation (MD) of four top-ranked compounds and X77 as co-crystal ligand were investigated.

Based on molecular docking studies, four compounds DB00224, DB00220, DB01232 and DB08873 exhibited the best results among compounds against M<[pro] enzyme. Additionally, molecular dynamic simulation and free binding energy were accomplished to compute the interaction energies and stability of the top-ranked compounds at the active site. The binding energy portions of the compounds into the enzyme active site exposed that Van der Waals and non-polar interactions were fundamental factors in the molecule binding. The ligand connections were steadied via hydrophobic interactions and several key hydrogen bonds especially with Glu166 and His41 residues into the active site.

According to calculations of docking and MD, it was observed that the active site is mostly hydrophobic. Additionally, the results showed the steady of selected ligands binding with SARS-CoV-2 M<[pro] active site.

The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19.

In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method for discovering novel drug candidates as potential COVID-19 main protease (Mpro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 Mpro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease.

Nineteen compounds were introduced as new potential inhibitors. Compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carbox- amide showed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 Mpro comparing to peramivir (-9.8 kcal/mol) as a positive control.

Based on these findings, nineteen compounds were proposed as possible new COVID-19 inhibitors, of which ZINC08765174 had a high affinity to Mpro. Furthermore, the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for the treatments of COVID-19.