Coronaviruses - Volume 5, Issue 1, 2024

The COVID-19 infection is rapidly spreading worldwide. Treating this new viral infection is a great challenge worldwide. There is no specific and approved medication for its treatment, so some medications are considered off-label. Antivirals, corticosteroids, antimalarial agents, and antibiotics are proposed in different countries to treat COVID-19. This narrative review discussed the off-label use of medications for COVID-19 and the beneficial and adverse effects of them. Evidence was collected and sorted from the literature ranging from 2019 to 2022 on scientific databases such as Web of Science, PubMed, and Scopus with suitable keywords. All papers, namely systematic reviews, case studies, and clinical guidelines, were evaluated. Antimalarial agents, antivirals, antibiotics, corticosteroids, NSAIDs, biological medicines, Ivermectin, and melatonin were reviewed in this study. Some medications have direct antiviral effects, and many can reduce infection symptoms and hospitalization. In some clinical trial trials, even some of them, such as corticosteroids, can lower death rates, particularly during the cytokine storm period. However, the effectiveness of some medications has not been understood. Besides, the side effects of off-label use of these medications must be considered a serious concern. There are no proven medications for COVID-19 yet. Off-label use of medications is a double-edged sword that can have advantages outweighing its disadvantages. The COVID-19 crisis taught us many lessons about dealing with health-related crises and their treatment management. One of the most important lessons is paying more attention to the discovery and development of novel drugs and vaccines based on modern technology.

Background: Mpro protease, an enzyme found in coronaviruses (PDB codes: 6LU7 and 2GTB), provides a unique way to recognize potentially active substances. All of the suggested drugs shared an ethanolamine/propylamine bridge, consisting of two to three lengths of carbon atoms, to treat COVID-19 patients. Because of this, the author chose to conduct the study using ascorbic acid, also known as R-5-(S)-1,2-dihydroxyethyl)-3,4-dihydroxyfuran-2(5H)-one, a potent immune system booster for combating coronavirus. Objective: In this study, ascorbic acid is used to identify new potential inhibitors of the SARS-CoV-2 Mpro enzyme using molecular docking, the Lipinski rule for drug-likeness, physiochemical property by Molinspiration, ADMET by Pre ADMET server, and Osiris property explorer for toxicity analysis in comparison to proposed drug therapy. Methods: The receptor-binding site in the active sites of Mpro protease (PDB codes: 6LU7 and 2GTB) was predicted using molecular docking studies using the GOLD, v5.2.2 program (Genetic Optimization for Ligand Docking). Ascorbic acid derivatives' physiochemical properties, druglikeness, ADME, and toxicity were further examined using Molinspiration, OSIRIS Property Explorer, and Pre ADMET service. Results: The findings result showed that molecules 16 and 17 had outstanding gold score/energy score with 6LU7 (52.45 & 51.45/-15.16 &-17.32 kJ/mol, respectively) and 2GTB (55.09 & 54.79/- 11.86 & -16.31 kJ/mol, respectively). All molecules were found with zero violation of Lipinski rules and showed good bioavailability via the oral route. In comparison to the proposed drugs, the compounds 3, 5, 6, 7, 8, 13, and 17 had good drug scores and received excellent drug-likeness ratings. The compounds 14, 15, 16, and 17 were observed as remarkable inhibitors for CYP 450 3A4, CYP 450 2C9 and CYP 450 2C19 and for CYP 450 3A4 and CYP 450 2D6. Conclusion: In the molecular docking study, compound 17 showed outstanding gold/energy values as well as excellent bioactivity scores against GPCR, protease inhibitors, and kinase inhibitors. Drugrelated attributes were obtained using OSIRIS property explorer and pre-ADME, which showed compound 17 to have an excellent drug score, no toxicity, and drug-likeness.

Background: Anti-inflammatory agents have been proposed to improve oxygenation and mortality rates in severe COVID-19 pneumonia. This study has assessed the impact of colchicine as a coadjuvant inflammatory agent to infliximab in adults hospitalized with severe COVID-19 pneumonia. Method: In this randomized, open-label clinical trial, 63 severe COVID-19 pneumonia patients according to the criteria of the National Institutes of Health, 18 to 85 years old, with an increase in TNF-α and IL-6 levels, were randomized to receive colchicine 1 mg for 7 days and infliximab as a single dose of 300 mg on the first day of treatment or infliximab as a single dose of 300 mg on the first day. The primary outcomes assessed were oxygenation parameters (PaO2/FiO2 ratio and lung infiltrate) after seven days, ICU and hospital length of stay, and in-hospital mortality rates. Secondary outcomes included laboratory data and drug safety after 7 days. Result: 52 patients with similar baseline characteristics completed the study. There were no significant differences in oxygenation parameters (PaO2/FiO2 ratio and lung infiltrate) after seven days, median ICU and hospital length of stay, and in-hospital mortality rates between the two groups. Laboratory data showed no differences between both the groups seven days after the treatment. Also, no serious side effects were observed during the study among the two groups, except for one patient, who experienced diarrhea. Conclusion: Our results cannot support the addition of colchicine to promote the improvement of clinical outcomes in severe COVID-19 pneumonia.

Introduction: During the COVID-19 pandemic, higher Enterococcus bloodstream infections (BSI) rates have been reported. To establish whether these infections actually increased, we compared the incidence of Enterococcal infections before (September 2019 to February 2020) and during the pandemic (April 2020 to March 2022). Materials and Methods: This retrospective observational study was conducted at a tertiary care center converted into a COVID-19 facility. All clinical samples received in our laboratory during the study period were included. Results: In the six months preceding the pandemic, 2,243 samples were positive for bacterial growth; of the isolated organisms, 100 were Enterococcus species. During the pandemic, 39 out of 996 positive samples were Enterococcus. E. faecium was the most common isolate, 79/99 and 37/39. BSI was the most common overall infection (554/996; 55.6%) compared to the period before it (287/2243; 12.79%). Enterococcus species accounted for 30 out of 554 (5.41%) BSI in COVID-19 patients and 21/287 in the period before it (7.31%). Ten out of 39 (25.64%) isolates were vancomycin-resistant compared to the pre-COVID-19 period (9/21; 42.8%). There was an increase in antimicrobial resistance in the pandemic, except for linezolid and high-level aminoglycoside. Conclusion: Although we noted a higher percentage of BSIs, Enterococci were isolated from a lesser rate of COVID-19 patients from our center compared to pre-pandemic times. The plausible reasons for this could be the protective gut microbiota in the Indian population, and no increase in Enterococcus species in the environment of patients.

Background: SARS-CoV-2 emerged in Wuhan in December 2019, and after that, it spread quickly around the world. The virus could spread to millions of individuals since there were no particular treatments or preventative measures. The COVID-19 infection is often treated with current drugs such as Remdesivir, steroids, tocilizumab, favipiravir, and ivermectin. However, the immunosuppressive effects of these medicines might worsen COVID-19 symptoms and put the lives of immunocompromised individuals in peril. Thus, it is important to sustain a robust immune system when undergoing therapy for COVID-19. Herbal treatment has the potential to accomplish this objective. Objective: The current investigation involves the preparation of polyherbal syrup containing various medicinal plants such as ephedra, diascorea, ginger, echinacea, garlic, rhubarb, and glycyrrhiza for the effective control of the COVID-19 infection. Methods: All varieties of the individual plant powders (200 g) were treated to a 7 day maceration in aqueous ethanol (70:30) in a percolator at room temperature with intermittent vigorous shaking at room temperature and storage of the extract in a dark room. The mixture was run through a muslin cloth and then a Whatman qualitative grade 1 filter paper to produce the filtrate. The filtrate was evaporated to a thick paste-like consistency at 370°C under decreased pressure in a rota evaporator connected to a vacuum pump. After that, each individual extract was collected and kept in airtight jars at 4°C. According to the Indian Pharmacopoeia, simple syrup (66.67% w/v) of polyherbal extract was prepared. The oral administration of polyherbal syrup was carried out at varied doses of 0.5 ml, 1 ml, and 1.5 ml to infected golden Syrian hamsters from the 7th day for one week after infection reached its peak. Results: When compared to the infection control group, the results revealed that the viral load was significantly reduced by 79.1% when treated with polyherbal syrup. A histological examination of the infected hamster lung on days 7, 10, and 13 demonstrated that polyherbal syrup significantly decreased viral load in a dose-dependent manner. Conclusion: It is inferred that the polyherbal syrup formulation demonstrates efficacy in the prevention of COVID-19 infection during its first stages and may serve as a potential contender for SARSCoV- 2 due to its immunomodulatory properties.

The COVID-19 pandemic has highlighted the critical importance of pandemic preparedness worldwide, following the devastating 1918 pandemic. The rapid spread of COVID-19, originating in China, led to its classification as a global pandemic by the World Health Organization. COVID-19 is a member of the Coronaviridae family, a large family of viruses that have undergone extensive mutation and evolution over time. Among the coronaviruses, SARS-CoV-2, a Betacoronavirus, has emerged as a highly virulent pathogen capable of causing severe illness and fatalities in both humans and animals. Since 1966, various types of coronaviruses have surfaced, each exhibiting distinct mutations and structural characteristics. These genetic changes have contributed to the enhanced potency of the virus, intensifying the global pandemic crisis we face today. In response, the pharmaceutical approach to combat COVID-19 encompasses a multifaceted strategy. This includes the development of novel antiviral drugs specifically targeting the virus, as well as the repurposing of existing medications to evaluate their effectiveness against the virus. Additionally, there is a growing interest in exploring the potential of herbal and traditional medicine in the treatment of COVID-19. Continued research and collaboration among scientists, healthcare professionals, and pharmaceutical companies are crucial in the quest to find effective treatments for COVID-19 and to mitigate the impact of future coronavirus outbreaks. It is imperative to recognize the power and adaptability of microorganisms, emphasizing the need for vigilance and caution in preventing and managing infectious diseases. By investing in robust pandemic preparedness, measures and fostering global cooperation, we can enhance our ability to respond effectively to emerging viral threats and safeguard public health.