A Web-Based Method for the Identification of IL6-Based Immunotoxicity in Vaccine Candidates.

Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, and cytokine storm in COVID-19 patients. Thus, it is extremely important to identify and remove the antigenic regions from a therapeutic protein or vaccine candidate that may induce IL6-associated immunotoxicity. In order to overcome this challenge, our group has developed a computational tool, IL6pred, for discovering IL6-inducing peptides in a vaccine candidate. The aim of this chapter is to describe the potential applications and methodology of IL6pred. It sheds light on the prediction, designing, and scanning modules of IL6pred webserver and standalone package ( https://webs.iiitd.edu.in/raghava/il6pred/ ).

Status and consolidated list of threatened medicinal plants of India.

A wide array of medicinal plants in India, primarily used by locals for health care, have found wide acceptance and adoption globally (either directly or processed) due to distinct advantages of good results, low or no side-effects and ease of access to general public. Indigenous and traditional systems of medicine in practice since historical times have shown potential (direct or indirect as immune-boosters) against many dreaded ailments including the recent global pandemic of COVID-19. With prediction of sixth mass extinction, there is worldwide concern as majority of these plants, collected from natural stands, are also facing threat of extinction. Since 1990s concerted efforts have been directed towards assessment of threat status, the basic requirement for prioritizing conservation activity to various species of plants and animals. In literature there is staggered information regarding list of threatened plants, including medicinal plants of India, compiled at either state level or national or international level. Analysis of these publications led to collation of a consolidated list of 84 species and the same is presented here. A brief account of conservation efforts in India at national level and supportive policy framework is also included. This compilation is aimed to serve as a comprehensive reference especially for beginners, researchers, conservationists, foresters, pharmaceutical professionals as well as policy makers.

Focusing COVID-19-associated mucormycosis: a major threat to immunocompromised COVID-19.

COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals recovering from COVID-19. Mucormycosis has emanated as an outcome of the recent COVID-19 pandemic outbreak as rapidly developing fatal illness which was acquired by Mucorales fungus which is a subcategory of molds known as mucormycetes. Mucormycosis is one of the serious, sporadic mycotic illnesses which is a great threat to immunocompromised COVID-19 patients and affects people of all ages, including children with COVID-19 infections. This is associated with tissue damaging property and, therefore, causes serious clinical complications and elevated death rate. The COVID-19-associated mucormycosis or "black fungus" are the terms used interchangeably. The rapid growth of tissue necrosis presenting as "rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated disease" are various clinical forms of mucormycosis. The patient's prognosis and survival can be improved with proper surgeries using an endoscopic approach for local tissue protection in conjunction with course of appropriate conventional antifungal drug like Amphotericin-B and novel drugs like Rezafungin, encochleated Amphotericin B, Orolofim, and SCY-078 which have been explored in last few years. This review provides an overview of mucormycosis including its epidemiology, pathophysiology, risk factors, its clinical forms, and therapeutic approaches for disease management like antifungal therapy, surgical debridement, and iron chelators. The published patents and ongoing clinical trials related to mucormycosis have also been mentioned in this review.

A motley of possible therapies of the COVID-19: reminiscing the origin of the pandemic.

The 2019 outbreak of corona virus disease began from Wuhan (China), transforming into a leading pandemic, posing an immense threat to the global population. The WHO coined the term nCOVID-19 for the disease on 11th February, 2020 and the International Committee of Taxonomy of Viruses named it SARS-CoV-2, on account of its similarity with SARS-CoV-1 of 2003. The infection is associated with fever, cough, pneumonia, lung damage, and ARDS along with clinical implications of lung opacities. Brief understanding of the entry target of virus, i.e., ACE2 receptors has enabled numerous treatment options as discussed in this review. The manuscript provides a holistic picture of treatment options in COVID-19, such as non-specific anti-viral drugs, immunosuppressive agents, anti-inflammatory candidates, anti-HCV, nucleotide inhibitors, antibodies and anti-parasitic, RNA-dependent RNA polymerase inhibitors, anti-retroviral, vitamins and hormones, JAK inhibitors, and blood plasma therapy. The text targets to enlist the investigations conducted on all the above categories of drugs, with respect to the COVID-19 pandemic, to accelerate their significance in hindering the disease progression. The data collected primarily targets recently published articles and most recent records of clinical trials, focusing on the last 10-year database. The current review provides a comprehensive view on the critical need of finding a suitable treatment for the currently prevalent COVID-19 disease, and an opportunity for the researchers to investigate the varying possibilities to find and optimized treatment approach to mitigate and ameliorate the chaos created by the pandemic worldwide.

Targeting natural products against SARS-CoV-2.

The human coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Natural products, secondary metabolites show positive leads with antiviral and immunotherapy treatments using genomic studies in silico docking. In addition, it includes the action of a mechanism targeting the SARS-CoV-2. In this literature, we aimed to evaluate the antiviral movement of the NT-VRL-1 unique terpene definition to Human coronavirus (HCoV-229E). The effects of 19 hydrolysable tannins on the SARS-CoV-2 were therefore theoretically reviewed and analyzed utilising the molecular operating surroundings for their C-Like protease 3CLpro catalytic dyad residues Angiotensin converting enzyme-2 (MOE 09). Pedunculagin, tercatan, and castalin were detected as interacting strongly with SARS-receptor Cov-2's binding site and catalytic dyad (Cys145 and His41). SARS-CoV-2 methods of subunit S1 (ACE2) inhibit the interaction of the receiver with the s-protein once a drug molecule is coupled to the s-protein and prevent it from infecting the target cells in alkaloids. Our review strongly demonstrates the evidence that natural compounds and their derivatives can be used against the human coronavirus and serves as an area of research for future perspective.

COVID-19 and diabetes: Association intensify risk factors for morbidity and mortality.

Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.

Digital Moral Outrage, Collective Guilt, And Collective Action: An Examination of How Twitter Users Expressed Their Anguish During India's Covid-19 Related Migrant Crisis.

This paper examines the intersection of group-based expressions including digital moral outrage, collective guilt, and collective action on Twitter, following the tragic incident of 8 May 2020, in which 16 migrant workers were run over by a train after the Indian government imposed a sudden COVID-19-related lockdown. Twitter data were gathered immediately at three different times - May 8-15, May 16- 23, May 24-May 31, and 4598 tweets were manually coded. The analysis revealed that digital moral outrage was the most frequently expressed emotion. It, however, gradually decreased, signaling digital outrage fatigue. Collective guilt and sympathy constituted the second-largest portion of the total tweets, and tweets reflecting collective action by the community progressively increased. The network of relationships among different group-based emotions, the promotion of one-sided narratives and virtue signaling on social media platforms are discussed.

There is nothing exempt from the peril of mutation - The Omicron spike.

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets - kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways - on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Referrals to liaison services for older adults with deliberate self harm during the SARS-CoV-2 national lockdown - a collaborative service evaluation using liaison referral data

Aims Social isolation and living alone have been associated with increased suicidality in older adults. During the SARS-CoV-2 pandemic, older adults were advised to keep isolated and maintain social distancing. Lockdown periods in England may have led to increased isolation and loneliness in older people, possibly resulting in an increased rates of DSH and suicide. This study aimed to explore whether numbers of older adults referred to liaison services with deliberate self harm changed during the SARS-CoV-2 pandemic. Method Reason for referral and total number of referrals to liaison services for older adults data were collected across 6 mental health trusts who had access to robust data sets. Data were collected prospectively for three months from the start of the UK national lockdown and for the corresponding 3 month period in 2019, via trust reporting systems. This study was registered as service evaluation within each of the participating mental health trusts. Result Overall numbers of referrals to older adult liaison services went down, but the proportion of referrals for older adults with DSH increased. Across the six mental health trusts there there were a total of 2167 referrals over the first three month lockdown period in 2020, and 170 (7.84%) of these referrals were for deliberate self harm. During a corresponding time period in 2019, there were a total of 3416 referrals and 155 (4.54%) of these referrals were for deliberate self harm Conclusion Although numbers of referrals for older adults with delberate self harm appeared to stay the same, the severity of these presentations is not clear. Outcomes of referrals and severity of self harm could be explored by examining individual case records. As there have been subsequent lockdowns the data collection period should also be extended to include these. Triangulation with national and local datasets on completed suicide is planned.

CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target.

The combat against the Corona virus disease of 2019 (COVID-19), has created a chaos among the healthcare institutions and researchers, in turn accelerating the dire need to curtail the infection spread. The already established entry mechanism, via ACE2 has not yet successfully aided in the development of a suitable and reliable therapy. Taking in account the constant progression and deterioration of the cases worldwide, a different perspective and mechanistic approach is required, which has thrown light onto the cluster of differentiation 147 (CD147) transmembrane protein, as a novel route for SARS-CoV-2 entry. Despite lesser affinity towards COVID-19 virus, as compared to ACE2, this receptor provides a suitable justification behind elevated blood glucose levels in infected patients, retarded COVID-19 risk in women, enhanced susceptibility in geriatrics, greater infection susceptibility of T cells, infection prevalence in non-susceptible human cardiac pericytes and so on. The manuscript invokes the title role and distribution of CD147 in COVID-19 as an entry receptor and mediator of endocytosis-promoted entry of the virus, along with the "catch and clump" hypothesis, thereby presenting its Fundamental significance as a therapeutic target for potential candidates, such as Azithromycin, melatonin, statins, beta adrenergic blockers, ivermectin, Meplazumab etc. Thus, the authors provide a comprehensive review of a different perspective in COVID-19 infection, aiming to aid the researchers and virologists in considering all aspects of viral entry, in order to develop a sustainable and potential cure for the 2019 COVID-19 disease.

Anticipated pharmacological role of Aviptadil on COVID-19.

Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.

Linking COVID-19 and Parkinson's disease: Targeting the role of Vitamin-D.

COVID-19 pandemic has a major effect on world health, particularly on individuals suffering from severe diseases or old aged persons. Various case studies revealed that COVID-19 might increase the progression of Parkinson's disease (PD). Coxsackievirus, dengue virus Epstein-Barr virus, hepatitis C virus, Japanese encephalitis, Western equine encephalomyelitis virus, West Nile virus, and human immunodeficiency virus have all been linked to the development of transient or permanent parkinsonism, owing to the induction of neuroinflammation/hypoxic brain injury with structural/functional damage within the basal ganglia. Coronavirus mainly infects the alveolar cells and may lead to acute respiratory distress syndrome. SARS-CoV-2 invades cells via the ACE2 receptor, which is widely expressed in the central nervous system, where the virus may precipitate or accelerate dementia. SARS-CoV-2 could enter the central nervous system directly by the olfactory/vagus nerves or through the bloodstream. Here, we talked about the importance of this viral infection in terms of the CNS as well as its implications for people with Parkinson's disease; anosmia & olfaction-related impairments in COVID-19 & PD patients. And, also discussed the role of vitamin D to sustain the progression of Parkinson's disease and the COVID-19; regular vitamin D3 consumption of 2000-5000 IU/day may reduce the risk and severity of COVID-19 in parkinsonian patients.

Computer-aided prediction of inhibitors against STAT3 for managing COVID-19 associated cytokine storm.

BACKGROUND: Proinflammatory cytokines are correlated with the severity of disease in patients with COVID-19. IL6-mediated activation of STAT3 proliferates proinflammatory responses that lead to cytokine storm promotion. Thus, STAT3 inhibitors may play a crucial role in managing the COVID-19 pathogenesis. The present study discusses a method for predicting inhibitors against the STAT3 signaling pathway. METHOD: The main dataset comprises 1565 STAT3 inhibitors and 1671 non-inhibitors used for training, testing, and evaluation of models. A number of machine learning classifiers have been implemented to develop the models. RESULTS: The outcomes of the data analysis show that rings and aromatic groups are significantly abundant in STAT3 inhibitors compared to non-inhibitors. First, we developed models using 2-D and 3-D chemical descriptors and achieved a maximum AUC of 0.84 and 0.73, respectively. Second, fingerprints are used to build predictive models and achieved 0.86 AUC with an accuracy of 78.70% on the validation dataset. Finally, models were developed using hybrid descriptors, which achieved a maximum of 0.87 AUC with 78.55% accuracy on the validation dataset. CONCLUSION: We used the best model to identify STAT3 inhibitors in FDA-approved drugs and found few drugs (e.g., Tamoxifen and Perindopril) to manage the cytokine storm in COVID-19 patients. A webserver "STAT3In" (https://webs.iiitd.edu.in/raghava/stat3in/) has been developed to predict and design STAT3 inhibitors.

Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19.

Interleukin 6 (IL-6) is a pro-inflammatory cytokine that stimulates acute phase responses, hematopoiesis and specific immune reactions. Recently, it was found that the IL-6 plays a vital role in the progression of COVID-19, which is responsible for the high mortality rate. In order to facilitate the scientific community to fight against COVID-19, we have developed a method for predicting IL-6 inducing peptides/epitopes. The models were trained and tested on experimentally validated 365 IL-6 inducing and 2991 non-inducing peptides extracted from the immune epitope database. Initially, 9149 features of each peptide were computed using Pfeature, which were reduced to 186 features using the SVC-L1 technique. These features were ranked based on their classification ability, and the top 10 features were used for developing prediction models. A wide range of machine learning techniques has been deployed to develop models. Random Forest-based model achieves a maximum AUROC of 0.84 and 0.83 on training and independent validation dataset, respectively. We have also identified IL-6 inducing peptides in different proteins of SARS-CoV-2, using our best models to design vaccine against COVID-19. A web server named as IL-6Pred and a standalone package has been developed for predicting, designing and screening of IL-6 inducing peptides (https://webs.iiitd.edu.in/raghava/il6pred/).

A Web-Based Platform on Coronavirus Disease-19 to Maintain Predicted Diagnostic, Drug, and Vaccine Candidates.

A web-based resource CoronaVIR (https://webs.iiitd.edu.in/raghava/coronavir/) has been developed to maintain the predicted and existing information on coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have integrated multiple modules, including "Genomics," "Diagnosis," "Immunotherapy," and "Drug Designing" to understand the holistic view of this pandemic medical disaster. The genomics module provides genomic information of different strains of this virus to understand genomic level alterations. The diagnosis module includes detailed information on currently-in-use diagnostics tests as well as five novel universal primer sets predicted using in silico tools. The Immunotherapy module provides information on epitope-based potential vaccine candidates (e.g., LQLPQGTTLPKGFYA, VILLNKHIDAYKTFPPTEPKKDKKKK, EITVATSRTLS, GKGQQQQGQTV, SELVIGAVILR) predicted using state-of-the-art software and resources in the field of immune informatics. These epitopes have the potential to activate both adaptive (e.g., B cell and T cell) and innate (e.g., vaccine adjuvants) immune systems as well as suitable for all strains of SARS-CoV-2. Besides, we have also predicted potential candidates for siRNA-based therapy and RNA-based vaccine adjuvants. The drug designing module maintains information about potential drug targets, tertiary structures, and potential drug molecules. These potential drug molecules were identified from FDA-approved drugs using the docking-based approach. We also compiled information from the literature and Internet on potential drugs, repurposing drugs, and monoclonal antibodies. To understand host-virus interaction, we identified cell-penetrating peptides in the virus. In this study, state-of-the-art techniques have been used for predicting the potential candidates for diagnostics and therapeutics.