How to face COVID-19: proposed treatments based on remdesivir and hydroxychloroquine in the presence of zinc sulfate. Docking/DFT/POM structural analysis.

Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.

Pathogenesis and Management of COVID-19.

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

Public Perception towards Vaccines as Preventive Measures against a Twindemic (Seasonal Influenza and COVID-19): A Cross-Sectional Study from the Aseer Region, Saudi Arabia.

This study aimed to evaluate Saudi Arabian public perceptions toward influenza and COVID-19 immunization during the flu season. A cross-sectional self-administered, structured, and closed-questionnaire online survey was conducted on the general public. A total of 422 people willingly participated in the survey using several social media platforms from 15 May to 15 July 2021. Residents of Saudi Arabia aged 18 or older (eligible for COVID-19 vaccination) were included in the study and willing to answer questionnaires. The 422 participants who agreed to participate in the study completed the questionnaire. Thirty-seven percent of the participants were youth (18-25 years). More than 80% of the participants in the study agreed or strongly agreed that flu and COVID-19 vaccines must be mandatory for all populations. At the same time, 42.4% considered that the COVID-19 vaccine might positively impact the public and the economy in the future. Participants confirmed to have had COVID-19 or the flu since the beginning of the outbreak totaled 21.3%. Of the participants, 54% had sufficient knowledge about vaccine types and safety. Most of our participants (54.9%) agreed that preventive measures were still required, even with the existence of vaccines. Our study provides an overview of COVID-19's influence on Saudi Arabia during the flu season. The Saudi Arabian government should consider preventive efforts to strengthen confidence in the health advantages offered by prospective immunization to prevent a twindemic of influenza and COVID-19.

Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach.

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. Mpro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making Mpro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of -8.3, -8.6, and -8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.

Attitude and Willingness to Get COVID-19 Vaccines by a Community Pharmacist in Saudi Arabia: A Cross-Sectional Study.

Introduction: Community pharmacists play a key role as vaccinators for COVID-19. They can reduce the burden of the disease worldwide. Objective: This study used a cross-sectional questionnaire to determine whether the Saudi Arabian public was willing to obtain the COVID-19 vaccine via community pharmacists. Results: The questionnaire focused on the satisfaction, concerns, and opinions towards providing vaccination by community pharmacists. The study featured 415 individuals aged 18 and older (eligible for the COVID-19 vaccine). Of the participants in this study, 58.1% were aged 18-25, with 55.4% female. Most participants (72.8%) have not been exposed to COVID-19 and are not aware of the approval of COVID-19 vaccination by community pharmacists. Of the 415 complete questionnaires, 45% believed that community pharmacists are not experienced in administering vaccines. However, 63% of participants are satisfied with getting the COVID-19 vaccination by a community pharmacist if no other option is available. More than 68% of the respondents agree that community pharmacies should expand their health care services to include vaccinations, prescriptions, checkups, and other forms of preventative medicine. Discussion: The availability of community pharmacist-administered vaccination in Saudi Arabia could be a significant factor in the success of the country's vaccination program. This study may serve as a model to expand the role of pharmacists in other countries' vaccination programs.

A Novel Multicolor-thresholding Auto-detection Method to Detect the Location and Severity of Inflammation in Confirmed SARS-COV-2 Cases using Chest X-Ray Images.

OBJECTIVES: Since late 2019, Coronavirus Disease 2019 (COVID-19) has spread around the world. It has been determined that the disease is very contagious and can cause Acute Respiratory Distress (ARD). Medical imaging has the potential to help identify, detect, and quantify the severity of this infection. This work seeks to develop a novel auto-detection technique for verified COVID-19 cases that can detect aberrant alterations in traditional X-ray pictures. METHODS: Nineteen separately colored layers were created from X-ray scans of patients diagnosed with COVID-19. Each layer represents objects that have a similar contrast and can be represented by a single color. In a single layer, objects with similar contrasts are formed. A single color image was created by extracting all the objects from all the layers. The prototype model could recognize a wide range of abnormal changes in the image texture based on color differentiation. This was true even when the contrast values of the detected unclear abnormalities varied slightly. RESULTS: The results indicate that the proposed novel method is 91% accurate in detecting and grading COVID-19 lung infections compared to the opinions of three experienced radiologists evaluating chest X-ray images. Additionally, the method can be used to determine the infection site and severity of the disease by categorizing X-rays into five severity levels. CONCLUSION: By comparing affected tissue to healthy tissue, the proposed COVID-19 auto-detection method can identify locations and indicate the severity of the disease, as well as predict where the disease may spread.

Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra02885e

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a contagious respiratory tract infection that has become a global burden since the end of 2019. Notably, fewer patients infected with SARS-CoV-2 progress from acute disease onset to death compared with the progression rate associated with two other coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Several research organizations and pharmaceutical industries have attempted to develop successful vaccine candidates for the prevention of COVID-19. However, increasing evidence indicates that the SARS-CoV-2 genome undergoes frequent mutation;thus, an adequate analysis of the viral strain remains necessary to construct effective vaccines. The current study attempted to design a multi-epitope vaccine by utilizing an approach based on the SARS-CoV-2 structural proteins. We predicted the antigenic T- and B-lymphocyte responses to four structural proteins after screening all structural proteins according to specific characteristics. The predicted epitopes were combined using suitable adjuvants and linkers, and a secondary structure profile indicated that the vaccine shared similar properties with the native protein. Importantly, the molecular docking analysis and molecular dynamics simulations revealed that the constructed vaccine possessed a high affinity for toll-like receptor 4 (TLR4). In addition, multiple descriptors were obtained from the simulation trajectories, including the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg), demonstrating the rigid nature and inflexibility of the vaccine and receptor molecules. In addition, codon optimization, based on Escherichia coli K12, was used to determine the GC content and the codon adaptation index (CAI) value, which further followed for the incorporation into the cloning vector pET28+(a). Collectively, these findings suggested that the constructed vaccine could be used to modulate the immune reaction against SARS-CoV-2. COVID-19 is caused by SARS-CoV-2, resulting in a contagious respiratory tract infection. For designing a multi-epitope vaccine, we utilized the four structural proteins from the SARS-CoV-2 by using bioinformatics and immunoinformatics analysis.

Acute Respiratory Distress Syndrome and COVID-19: A Literature Review.

Acute respiratory distress syndrome (ARDS) is an overwhelming inflammatory disorder of the lung due to direct and indirect insults to the lungs. ARDS is characterized by increased vascular permeability, protein-rich edema, diffuse alveolar infiltrate, and loss of aerated lung tissue, leading to decreased lung compliance, tachypnea, and severe hypoxemia. COVID-19 is generally associated with ARDS, and it has gained prime importance since it started. The mortality rate is alarmingly high in COVID-19-related ARDS patients regardless of advances in mechanical ventilation. Several pharmacological agents, including corticosteroids, nitric oxide, neuromuscular blocker, anti-TNF, statins, and exogenous surfactant, have been studied and some are under investigation, like ketoconazole, lisofylline, N-acetylcysteine, prostaglandins, prostacyclin, and fish oil. The purpose of this review is to appraise the understanding of the pathophysiology of ARDS, biomarkers, and clinical trials of pharmacological therapies of ARDS and COVID-19-related ARDS.

The Impact of Social Media on the Acceptance of the COVID-19 Vaccine: A Cross-Sectional Study from Saudi Arabia.

INTRODUCTION: Social media platforms are used by many people to seek and share health-related information that may influence their decision-making about COVID-19 vaccination. PURPOSE: The objective of this study is to understand the influence of social media on the attitudes and willingness of the general public of the Aseer region of Saudi Arabia to receive COVID-19 vaccination. MATERIALS AND METHODS: A cross-sectional self-administrated online survey was conducted in Saudi Arabia Aseer region, where 613 persons willingly took part in the survey in April and May 2021. Residents of Aseer in Saudi Arabia, who are over the age of 18 (eligible for COVID-19 vaccination) and willing to participate in the survey, were included in the study. RESULTS: Overall, 74.6% agreed that the COVID-19 vaccine was misrepresented via social media. However, 37% of those respondents strongly agreed that social media had increased their willingness to get the COVID-19 vaccine. In addition, employees reported (21.8%) or strongly agreed (28%) that the quantity and quality of information on social media has a detrimental impact on their psychological well-being. Additionally, participants also agreed (21.8%) or strongly agreed (28%) that social media had a negative effect on their psychological condition. CONCLUSION: The study provides that there was a high degree of awareness indicated among Aseer population regarding misleading information about COVID-19 vaccination via social media. Thus, social media that can share up-to-date scientific information about vaccination must be utilized optimally by the government to assist people in making decisions about accepting vaccinations.

An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants.

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

Appraisals of the Bangladeshi Medicinal Plant Calotropis gigantea Used by Folk Medicine Practitioners in the Management of COVID-19: A Biochemical and Computational Approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized in Wuhan in late 2019 and, since then, had spread globally, eventually culminating in the ongoing pandemic. As there is a lack of targeted therapeutics, there is certain opportunity for the scientific community to develop new drugs or vaccines against COVID-19 and so many synthetic bioactive compounds are undergoing clinical trials. In most of the countries, due to the broad therapeutic spectrum and minimal side effects, medicinal plants have been used widely throughout history as traditional healing remedy. Because of the unavailability of synthetic bioactive antiviral drugs, hence all possible efforts have been focused on the search for new drugs and alternative medicines from different herbal formulations. In recent times, it has been assured that the Mpro, also called 3CLpro, is the SARS-CoV-2 main protease enzyme responsible for viral reproduction and thereby impeding the host's immune response. As such, Mpro represents a highly specified target for drugs capable of inhibitory action against coronavirus disease 2019 (COVID-19). As there continue to be no clear options for the treatment of COVID-19, the identification of potential candidates has become a necessity. The present investigation focuses on the in silico pharmacological activity of Calotropis gigantea, a large shrub, as a potential option for COVID-19 Mpro inhibition and includes an ADME/T profile analysis of that ligand. For this study, with the help of gas chromatography-mass spectrometry analysis of C. gigantea methanolic leaf extract, a total of 30 bioactive compounds were selected. Our analyses unveiled the top four options that might turn out to be prospective anti-SARS-CoV-2 lead molecules; these warrant further exploration as well as possible application in processes of drug development to combat COVID-19.

Of mitochondrion and COVID-19.

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.

Prospective Role of Peptide-Based Antiviral Therapy Against the Main Protease of SARS-CoV-2.

The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex's stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2.

Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A New Route in the Fight Against COVID-19?

Cannabis sativa is a well-known plant that has been recognized for its benefits since ancient times by several medicinal systems, including those of China, India, Greece, and Egypt. Although C. sativa is one of the most investigated medicinal plants in the world, it faces some of the greatest controversies surrounding its legalization and use as a medication. C. sativa contains several hundred phytoconstituents, including the infamous "cannabinoids". It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where cannabis is still facing legal obstacles. The current review focuses on the most recent literature pertaining to various applications of cannabinoids, with a special focus on the medicinal aspect of these phytochemicals. Peer-reviewed articles focusing on the importance of cannabis and cannabinoids are the target of this review. Articles were selected based on the relevance to the general scope of the work, i.e., application of cannabinoids. Cannabinoids can truly be regarded as wonder drugs, considering their immense diversity of usage. Unfortunately, however, many of the mares have never been researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizon for the use of these natural drugs in medicines such as Epidiolex® (cannabidiol, used for the treatment of severe forms of epilepsy) and Sativex®(Δ9-tetrahydrocannabinol and cannabidiol, used for the treatment of spasticity caused by multiple sclerosis). Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive component. This review addresses the most important applications or current utilization of cannabinoids in a variety of treatments such as chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicable diseases, glaucoma, and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, cannabis has a myriad of bioactive compounds that have the potential to increase the list of approved cannabinoids suitable for therapy.