SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19.

The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.

Crosstalk Between SARS-CoV-2 Infection and Neurological Disorders: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for coronavirus disease (COVID-19), is an issue of global concern since March 2020. The respiratory manifestations of COVID-19 have widely been explained in the last couple of months of the pandemic. Initially, the virus was thought to be restricted to the pulmonary system; however, as time progressed and cases increased during the second wave of COVID-19, the virus affected other organs, including the nervous system. The neurological implication of SARS-CoV-2 infection is mounting, as substantiated by various reports, and in the majority of COVID-19 patients with neurological symptoms, the penetration of SARS-CoV-2 in the central nervous system (CNS) is likely. SARS-CoV-2 can enter the nervous system by exploiting the routes of olfactory mucosa, olfactory, and sensory nerve endings, or endothelial and nerve tissues, thus crossing the neural-mucosal interface in the olfactory mucosa in the nose. Owing to multifactorial and complex pathogenic mechanisms, COVID-19 adds large-scale risk to the entire nervous system. A thorough understanding of SARS-CoV-2 neurological damage is still vague; however, our comprehension of the virus is rapidly developing. The present comprehensive review will gain insights and provide neurological dimensions of COVID-19 and their associated anomalies. The review presents the entry routes of SARS-CoV-2 into the CNS, to ascertain potential targets in the tissues owing to infection. We also discuss the molecular mechanisms involved, the array of clinical symptoms, and various nervous system diseases following the attack of SARS-CoV-2.

miRNAs in SARS-CoV-2 Infection: An Update.

Coronavirus disease-2019 (COVID-19) is a highly infectious disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the inception of SARS-CoV-2 in Wuhan, China, the virus has traveled more than 200 countries globally. The role of SARS-CoV-2 in COVID-19 has been thoroughly investigated and reviewed in the last 22 months or so; however, a comprehensive outline of miRNAs in SARS-CoV- 2 infection is still missing. The genetic material of SARS-CoV-2 is a single-stranded RNA molecule nearly 29 kb in size. RNA is composed of numerous sub-constituents RNA is found in the cells in a number of forms. including microRNAs (miRNAs). miRNAs play an essential role in biological processes like apoptosis, cellular metabolism, cell death, cell movement, oncogenesis, intracellular signaling, immunity, and infection. Lately, miRNAs have been involved in SARS-CoV-2 infection, though the clear demonstration of miRNAs in the SARS-CoV-2 infection is not fully elucidated. The present review article summarizes recent findings of miRNAs associated with SARS-CoV-2 infection. We presented various facets of miRNAs. miRNAs as the protagonists in viral infection, the occurrence of miRNA in cellular receptors, expression of miRNAs in multiple diseases, miRNA as a biomarker, and miRNA as a therapeutic tool have been discussed in detail. We also presented the vaccine status available in various countries.

Comparative highlights on MERS-CoV, SARS-CoV-1, SARS-CoV-2, and NEO-CoV.

The severe acute respiratory syndrome (SARS-CoV, now SARS-CoV-1), middle east respiratory syndrome (MERS-CoV), Neo-CoV, and 2019 novel coronavirus (SARS-CoV-2/COVID-19) are the most notable coronaviruses, infecting the number of people worldwide by targeting the respiratory system. All these viruses are of zoonotic origin, predominantly from bats which are one of the natural reservoir hosts for coronaviruses. Thus, the major goal of our review article is to compare and contrast the characteristics and attributes of these coronaviruses. The SARS-CoV-1, MERS-CoV, and COVID-19 have many viral similarities due to their classification, they are not genetically related. COVID-19 shares approximately 79 % of its genome with SARS-CoV-1 and about 50 % with MERS-CoV. The shared receptor protein, ACE2 exhibit the most striking genetic similarities between SARS-CoV-1 and SARS-CoV-2. SARS-CoV primarily replicates in the epithelial cells of the respiratory system, but it may also affect macrophages, monocytes, activated T cells, and dendritic cells. MERS-CoV not only infects and replicates inside the epithelial and immune cells, but it may lyse them too, which is one of the common reasons for MERS's higher mortality rate. The details of infections caused by SARS-CoV-2 and lytic replication mechanisms in host cells are currently mysterious. In this review article, we will discuss the comparative highlights of SARS-CoV-1, MERS-CoV, SARS-CoV-2, and Neo-CoV, concerning their structural features, morphological characteristics, sources of virus origin and their evolutionary transitions, infection mechanism, computational study approaches, pathogenesis and their severity towards several diseases, possible therapeutic approaches, and preventive measures.

Tetraspanin-enriched Microdomain Containing CD151, CD9, and TSPAN 8 - Potential Mediators of Entry and Exit Mechanisms in Respiratory Viruses Including SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, the Hubei region of China, has become a pandemic worldwide. It can transmit through droplets and enter via oral, nasal, and eye mucous membranes. It consists of single-stranded RNA (positive-sense), nonstructural proteins including enzymes and transcriptional proteins, and structural proteins such as Spike, Membrane, Envelope, and Nucleocapsid -proteins. SARS-CoV-2 mediates S-proteins entry and exit via binding to host cell surface proteins like tetraspanins. The transmembrane tetraspanins, CD151, CD9, and tetraspanin 8 (TSPAN8), facilitate the entry of novel coronaviruses by scaffolding host cell receptors and proteases. Also, CD151 was reported to increase airway hyperresponsiveness to calcium and nuclear viral export signaling. They may facilitate entry and exit by activating the serine proteases required to prime S-proteins in tetraspanin-enriched microdomains (TEMs). This article updates recent advances in structural proteins, their epitopes and putative receptors, and their regulation by proteases associated with TEMs. This review furnishes recent updates on the role of CD151 in the pathophysiology of SARS-CoV-2. We describe the role of CD151 in a possible mechanism of entry and exit in the airway, a major site for infection of SARS-CoV-2. We also updated current knowledge on the role of CD9 and TSPAN 8 in the entry and exit mechanism of coronaviruses. Finally, we discussed the importance of some small molecules which target CD151 as possible targeted therapeutics for COVID-19. In conclusion, this study could identify new targets and specific therapeutics to control emerging virus infections.

Cytokine storm and neuropathological alterations in patients with neurological manifestations of COVID-19.

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 IL-8, IL-10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients, which may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19 associated neuroinflammation, in the context of COVID-19 associated cytokine storm. While the short-term implications of this condition are extensively documented, its long-term implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk to develop neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.

Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Encephalitis in Patients with COVID-19: A Systematic Evidence-Based Analysis.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly infects the respiratory system, several investigations have shown the involvement of the central nervous system (CNS) along the course of the illness, with encephalitis being one of the symptoms. The objective of this systematic review was to evaluate the characteristics (clinical, neuro-radiological aspects, and laboratory features) and outcomes of encephalitis in COVID-19 patients. PubMed, Scopus, and Google Scholar databases were searched from 1 December 2019 until 21 July 2022 to identify case reports and case series published on COVID-19 associated with encephalitis. The quality of the included studies was assessed by the Joanna Briggs Institute critical appraisal checklists. This systematic review included 79 studies, including 91 COVID-19 patients (52.7% male) experiencing encephalitis, where 85.6% were adults (49.3 ± 20.2 years), and 14.4% were children (11.2 ± 7.6 years). RT-PCR was used to confirm 92.2% of the COVID-19 patients. Encephalitis-related symptoms were present in 78.0% of COVID-19 patients at the time of diagnosis. In these encephalitis patients, seizure (29.5%), confusion (23.2%), headache (20.5%), disorientation (15.2%), and altered mental status (11.6%) were the most frequently reported neurologic manifestations. Looking at the MRI, EEG, and CSF findings, 77.6%, 75.5%, and 64.1% of the patients represented abnormal results. SARS-CoV-2-associated or -mediated encephalitis were the most common type observed (59.3%), followed by autoimmune encephalitis (18.7%). Among the included patients, 66.7% were discharged (37.8% improved and 28.9% fully recovered), whereas 20.0% of the reported COVID-19-positive encephalitis patients died. Based on the quality assessment, 87.4% of the studies were of high quality. Although in COVID-19, encephalitis is not a typical phenomenon, SARS-CoV-2 seems like a neuropathogen affecting the brain even when there are no signs of respiratory illness, causing a high rate of disability and fatality.

A Review of the Rational and Current Evidence on Colchicine for COVID-19.

The current coronavirus disease (COVID-19) pandemic has affected millions of individuals worldwide. Despite extensive research efforts, few therapeutic options currently offer direct clinical benefits for COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly high owing to the high viral transmission rates in several countries and the rise of various mutations in the SARS-CoV-2. One currently available and widely used drug that combines both anti-inflammatory and immunomodulatory actions is colchicine, which has been proposed as a possible treatment option for COVID-19. Colchicine still did not get much attention from the medical and scientific communities despite its antiinflammatory and immunomodulatory mechanisms of action and positive preliminary data from early trials. This literature review article provides the scientific rationale for repurposing colchicine as a potential therapy for COVID-19. Further, we summarize colchicine's mechanisms of action and possible roles in COVID-19 patients. Finally, we supplement this review with a summary of the doses, side effects, and early efficacy data from clinical trials to date. Despite the promising early findings from multiple observational and clinical trials about the potential of colchicine in COVID-19, the data from the RECOVERY trial, the largest COVID-19 randomized controlled trial (RCT) in the world, showed no evidence of clinical benefits in mortality, hospital stays, or disease progression (n = 11340 patients). However, multiple other smaller clinical trials showed significant clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence. At present, the drug should not be used except for investigational purposes.

COVID-19 diagnostic methods in developing countries.

COVID-19 has become one of the few leading causes of death and has evolved into a pandemic that disrupts everyone's routine, and balanced way of life worldwide, and will continue to do so. To bring an end to this pandemic, scientists had put their all effort into discovering the vaccine for SARS-CoV-2 infection. For their dedication, now, we have a handful of COVID-19 vaccines. Worldwide, millions of people are at risk due to the current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite the lack of clinically authorized antiviral medications and vaccines for COVID-19, clinical trials of many recognized antiviral agents, their combination, and vaccine development in patients with confirmed COVID-19 are still ongoing. This discovery gave us a chance to get immune to this disease worldwide and end the pandemic. However, the unexpected capacity of mutation of the SARS-CoV-2 virus makes it difficult, like the recent SAS-CoV-2 Omicron variant. Therefore, there is a great necessity to spread the vaccination programs and prevent the spread of this dreadful epidemic by identifying and isolating afflicted patients. Furthermore, several COVID-19 tests are thought to be expensive, time-consuming, and require the use of adequately qualified persons to be carried out efficiently. In addition, we also conversed about how the various COVID-19 testing methods can be implemented for the first time in a developing country and their cost-effectiveness, accuracy, human resources requirements, and laboratory facilities.

Current synopsis on siRNA therapeutics as a novel anti-cancer and antiviral strategy: Progress and challenges.

Currently, a popular era in nanomedicine is the implementation of RNA nanoparticles for various diseases and their diagnosis. RNA interference (RNAi) involves the arrangement of gene mediating mechanisms where coding and non-coding are carried out. The targeted control of gene utterance via siRNA system by nanocarriers showed an epic impact on modifying therapeutic efficacy. The article endeavours to highlight the mechanism of siRNA with concern to possible applications which are established on cancer therapy. In the current scenario to discuss the possible anti-viral effectiveness of nanoparticles with particular reference to SARS-CoV. Self-assembled nanoparticle (NP) is developed and it competently delivers to small interfering RNA (siRNA) intravenously to the tumour. The nanoparticle was found by mixing with siRNA, carrier, DNA, and lipids, preceded by after-change. Newly FDA appreciation of the first polymer-drug and additional ones in the clinically linked RNA polymer has to be highly therapeutic and diagnostic value. It has been established to be a particularly useful means for cell-type definite delivery of other RNA therapeutics like siRNA. While RNAi has helped speed up the discovery and understanding functions of a gene, it also has great potential as a therapeutic and potentially prophylactic modality. This article stated the development in the RNA polymer and also provides some examples of their diagnostic applications and therapeutics special emphasis on the anti-cancer and antiviral strategy. Patisiran and Givosiran are the recently approved si-RNA based products available in the market.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

Crosstalk between SARS-CoV-2 Infection and Type II Diabetes.

Since the outbreak of coronavirus disease (COVID-19) in Wuhan, China, triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) in late November 2019, spreading to more than 200 countries of the world, the ensuing pandemic to an enormous loss of lives, mainly the older population with comorbidities, like diabetes, cardiovascular disease, chronic obstructive pulmonary disease, obesity, and hypertension. Amongst these immune-debilitating diseases, SARS-CoV-2 infection is the most common in patients with diabetes due to the absence of a normal active immune system to fight the COVID-19. Recovery of patients having a history of diabetes from COVID-19 encounters several complications, and their management becomes cumbersome. For control of coronavirus, antiviral medications, glucose-lowering agents, and steroids have been carefully evaluated. In the present review, we discuss the crosstalk between SARS-CoV-2 infection and patients with a history of diabetes. We mainly emphasize the molecular factors that are involved in diabetic individuals recently infected by SARS-CoV-2 and developed COVID-19 disease. Lastly, we examine the medications available for the long-term management of diabetic patients with SARS-CoV-2 infection.

A global report on the dynamics of COVID-19 with quarantine and hospitalization: A fractional order model with non-local kernel.

In this paper, a compartmental mathematical model has been utilized to gain a better insight about the future dynamics of COVID-19. The total human population is divided into eight various compartments including susceptible, exposed, pre-asymptomatic, asymptomatic, symptomatic, quarantined, hospitalized and recovered or removed individuals. The problem was modeled in terms of highly nonlinear coupled system of classical order ordinary differential equations (ODEs) which was further generalized with the Atangana-Balaeanu (ABC) fractional derivative in Caputo sense with nonlocal kernel. Furthermore, some theoretical analyses have been done such as boundedness, positivity, existence and uniqueness of the considered. Disease-free and endemic equilibrium points were also assessed. The basic reproduction was calculated through next generation technique. Due to high risk of infection, in the present study, we have considered the reported cases from three continents namely Americas, Europe, and south-east Asia. The reported cases were considered between 1st May 2021 and 31st July 2021 and on the basis of this data, the spread of infection is predicted for the next 200 days. The graphical solution of the considered nonlinear fractional model was obtained via numerical scheme by implementing the MATLAB software. Based on the fitted values of parameters, the basic reproduction number ℜ0 for the case of America, Asia and Europe were calculated as ℜ0≈2.92819, ℜ0≈2.87970 and ℜ0≈2.23507 respectively. It is also observed that the spread of infection in America is comparatively high followed by Asia and Europe. Moreover, the effect of fractional parameter is shown on the dynamics of spread of infection among different classes. Additionally, the effect of quarantined and treatment of infected individuals is also shown graphically. From the present analysis it is observed that awareness of being quarantine and proper treatment can reduce the infection rate dramatically and a minimal variation in quarantine and treatment rates of infected individuals can lead us to decrease the rate of infection.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic.

Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

Natural Products for the Prevention and Control of the COVID-19 Pandemic: Sustainable Bioresources.

Background: The world has been unprecedentedly hit by a global pandemic which broke the record of deadly pandemics that faced humanity ever since its existence. Even kids are well-versed in the terminologies and basics of the SARS-CoV-2 virus and COVID-19 now. The vaccination program has been successfully launched in various countries, given that the huge global population of concern is still far behind to be vaccinated. Furthermore, the scarcity of any potential drug against the COVID-19-causing virus forces scientists and clinicians to search for alternative and complementary medicines on a war-footing basis. Aims and Objectives: The present review aims to cover and analyze the etiology and epidemiology of COVID-19, the role of intestinal microbiota and pro-inflammatory markers, and most importantly, the natural products to combat this deadly SARS-CoV-2 virus. Methods: A primary literature search was conducted through PubMed and Google Scholar using relevant keywords. Natural products were searched from January 2020 to November 2020. No timeline limit has been imposed on the search for the biological sources of those phytochemicals. Interactive mapping has been done to analyze the multi-modal and multi-target sources. Results and Discussion: The intestinal microbiota and the pro-inflammatory markers that can serve the prognosis, diagnosis, and treatment of COVID-19 were discussed. The literature search resulted in yielding 70 phytochemicals and ten polyherbal formulations which were scientifically analyzed against the SARS-CoV-2 virus and its targets and found significant. Retrospective analyses led to provide information about 165 biological sources that can also be screened if not done earlier. Conclusion: The interactive analysis mapping of biological sources with phytochemicals and targets as well as that of phytochemical class with phytochemicals and COVID-19 targets yielded insights into the multitarget and multimodal evidence-based complementary medicines.