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Nandeeta Samad,1 Siddhartha Dutta,2 Temitayo Eniola Sodunke,3 Adiba Fairuz,4 Ashmita Sapkota,5 Zannatul Ferdous Miftah,6 Iffat Jahan,7 Paras Sharma,8 Abdullahi Rabiu Abubakar,9 Adekunle Babajide Rowaiye,10 Angus Nnamdi Oli,10 Jaykaran Charan,2 Salequl Islam,11 Mainul Haque12 1Department of Public Health, North South University, Dhaka, 1229, Bangladesh; 2Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India; 3Department of Anatomy, University of Ilorin, Nigeria; 4Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh; 5Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; 6Department of Nutrition and Food Science, University of Dhaka, Dhaka, Bangladesh; 7Department of Physiology, Eastern Medical College, Cumilla, Bangladesh; 8Department of Pharmacognosy, BVM College of Pharmacy, Gwalior, India; 9Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University, Kano, Nigeria; 10Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria; 11Department of Microbiology, Jahangirnagar University, Savar, Dhaka, Bangladesh; 12Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, MalaysiaCorrespondence: Mainul HaqueUnit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur, 57000, MalaysiaTel +60109265543Email runurono@gmail.comAbstract: The outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), later named COVID-19 by the World Health Organization (WHO), was initiated at Wuhan, Hubei, China, and there was a rapid spread of novel SARS-CoV-2 and the disease COVID-19 in late 2019. The entire world is now experiencing the challenge of COVID-19 infection. However, still very few evidence-based treatment options are available for the prevention and treatment of COVID-19 disease. The present review aims to summarize the publicly available information to give a comprehensive yet balanced scientific overview of all the fat-soluble vitamins concerning their role in SARS-CoV-2 virus infection. The roles of different fat-soluble vitamins and micronutrients in combating SARS-CoV-2 infection have been recently explored in several studies. There are various hypotheses to suggest their use to minimize the severity of COVID-19 infection. These vitamins are pivotal in the maintenance and modulation of innate and cell-mediated, and antibody-mediated immune responses. The data reported in recent literature demonstrate that deficiency in one or more of these vitamins compromises the patients’ immune response and makes them more vulnerable to viral infections and perhaps worse disease prognosis. Vitamins A, D, E, and K boost the body’s defense mechanism against COVID-19 infection and specifically prevent its complications such as cytokine storm and other inflammatory processes, leading to increased morbidity and mortality overemphasis. However, more detailed randomized double-blind clinical pieces of evidence are required to define the use of these supplements in preventing or reducing the severity of the COVID-19 infection.Keywords: SARS-CoV-2, COVID-19, fat-soluble vitamins, micronutrients, immune response

Adekunle Babajide Rowaiye,1 Okiemute Ajiroghene Okpalefe,2 Olukemi Onuh Adejoke,3 Joyce Oloaigbe Ogidigo,4 Oluwakemi Hannah Oladipo,5 Amoge Chidinma Ogu,3 Angus Nnamdi Oli,1 Samson Olofinase,2 Onyekachi Onyekwere,6 Abdullahi Rabiu Abubakar,7 Dilshad Jahan,8 Salequl Islam,9 Siddhartha Dutta,10 Mainul Haque11 1Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria; 2Department of Genetics, Genomics, Bioinformatics, National Biotechnology Development Agency, Abuja, Nigeria; 3Department of Medical Biotechnology, National Biotechnology Development Agency, Abuja, Nigeria; 4Bioresources Development Centre, Abuja, National Biotechnology Development Agency, Abuja, Nigeria; 5Bioresources Development Centre, Ilorin, National Biotechnology Development Agency, Kwara State, Nigeria; 6Bioresources Development Centre, Ubulu-Uku, National Biotechnology Development Agency, Delta State, Nigeria; 7Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University, Kano, 700233, Nigeria; 8Department of Hematology, Asgar Ali Hospital, Gandaria, Dhaka, 1204, Bangladesh; 9Department of Microbiology, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh; 10Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India; 11Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur, 57000, MalaysiaCorrespondence: Mainul HaqueUnit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur, 57000, MalaysiaTel +60109265543Email runurono@gmail.comAbstract: The COVID-19 pandemic constitutes an arduous global health challenge, and the increasing number of fatalities calls for the speedy pursuit of a remedy. This review emphasizes the changing aspects of the COVID-19 disease, featuring the cytokine storm’s pathological processes. Furthermore, we briefly reviewed potential therapeutic agents that may modulate and alleviate cytokine storms. The literature exploration was made using PubMed, Embase, MEDLINE, Google scholar, and China National Knowledge Infrastructure databases to retrieve the most recent literature on the etiology, diagnostic markers, and the possible prophylactic and therapeutic options for the management of cytokine storm in patients hospitalized with COVID-19 disease. The causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), continually threatens the efficiency of the immune system of the infected individuals. As the first responder, the innate immune system provides primary protection against COVID-19, affecting the disease’s progression, clinical outcome, and prognosis. Evidence suggests that the fatalities associated with COVID-19 are primarily due to hyper-inflammation and an aberrant immune function. Accordingly, the magnitude of the release of pro-inflammatory cytokines such as interleukin (IL)-1, (IL-6), and tumor necrosis alpha (TNF-α) significantly differentiate between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for diagnosis and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. The prophylaxis and the rapid treatment of cytokine storm by clinicians will significantly enhance the fight against the dreaded COVID-19 disease.Keywords: COVID-19, SARS-CoV-2, cytokine storm, hyper-inflammation, fatality

In the month of December 2019, the outbreak of COVID-19 disease in China marked the beginning of a global health challenge and the urgent need to discover and design appropriate therapeutic agents. The causative agent, SARS-CoV-2 has a high rate of infectivity and its Main protease enzyme plays a major role in the replication mechanism of the virus. This study is aimed at prospecting for natural compounds that have strong binding affinity and the ability to inhibit the SARS-CoV-2 Main Protease. A library of 1,048 natural compounds (with zero violations for Lipinski and Veber rules) obtained from edible African plants were used for this study. These compounds were molecularly docked against the SARS-CoV-2 Main Protease and the results were screened with the docking score obtained from N3 (-7.8 kcal/mol), which is a co-crystallized ligand of the target protein. Further screening for molar refractivity, pharmacokinetic properties and bioactivity was done with SWISSADME, pKCSM, and Molinspiration webservers respectively. The binding site analyses were done using the PLIP and Fpocket webservers. Molecular dynamic studies and analyses of Apo and Holo structures of target protein were done with theGalaxy webserver. The lead compounds, Rhamnetin and Ellagic acid show better therapeutic prediction than the standard. Whilst Rhamnetin binds at the active site, Ellagic acid binds at another cavity with a probable allosteric effect as suggested by the molecular dynamic studies. Further tests are required to evaluate the SARS-CoV-2 Main protease inhibition properties of the lead compounds.