Vitamin D-A prominent immunomodulator to prevent COVID-19 infection.

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

Versatility of acetalated dextran in nanocarriers targeting respiratory diseases

Acetalated dextran is a chemically modified version of the FDA approved polysaccharide ‘dextran’, which serves as a perspective drug-delivery material for the pulmonary delivery of therapeutics owing to its biodegradability, sensitivity towards acidic pH for stimuli-sensitive drug release, high encapsulation efficacy, chemical conjugation with pharmaceuticals, and potency to cross the mucosal layer. Mainly, the aerosolized dry powder inhalation formulations of drug-loaded acetalated-dextran prove to be the frontrunner candidates for pulmonary delivery for the effective management of chronic respiratory diseases such as lymphangioleiomyomatosis, tularemia, and the contemporary COVID-19 pandemic. The presented communication provides a succinct account of the pulmonary drug delivery applications of acetalated dextran.

Autoantibodies and autoimmune disorders in SARS-CoV-2 infection: pathogenicity and immune regulation.

Coronavirus disease 2019 (COVID-19) is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. The aim of this review article is to establish an understanding about the relationship between autoimmune conditions and COVID-19 infections. Although majority of the population have been protected with vaccines against this virus, there is yet a successful curative medication for this disease. The use of autoimmune medications has been widely considered to control the infection, thus postulating possible relationships between COVID-19 and autoimmune diseases. Several studies have suggested the correlation between autoantibodies detected in patients and the severity of the COVID-19 disease. Studies have indicated that the SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. This review discusses the current scenario and future prospects of promising therapeutic strategies that may be employed to regulate such autoimmune conditions.

Antimicrobial peptides: A plausible approach for COVID-19 treatment.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). AREAS COVERED: This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. EXPERT OPINION: Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

Triumvirate to treat mucormycosis: Interplay of pH, metal ions and antifungal drugs

Mucormycosis is a rare fungal infection mainly affecting immunocompromised patients. Recently, an alarming rise in cases of mucormycosis was observed in patients undergoing COVID-19 treatment. Commonly, this fungal infection is caused by Rhizopus spp., Mucor spp., and Lichtheimia spp., although the genera of other Mucorales such as Saksenaea, Rhizomucor, Cunninghamella, and Apophysomyces may also be involved. A number of factors such as high concentration of zinc, iron and hypoxia induced acidosis promote the growth of fungi, thereby increasing the risk of mucormycosis multiple folds. Iron chelators (deferasirox and deferiprone) and zinc chelators (clioquinol, phenanthroline and N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethane-1,2-diamine) have been reported to inhibit the growth of fungi in a number of in vitro and animal studies. Correction of metabolic acidosis by administration of bicarbonate or glycine reduces the susceptibility of patients to the invasion by fungal species. However, these factors have largely been ignored while deciding the treatment strategy for mucormycosis and first line treatment for the management of mucormycosis continues to be the expensive lipid based formulation of amphotericin B. Treatment with isavuconazole which is proposed as the second choice is reported to be more cost effective. Therefore, it is proposed that a combination of antifungal agent (isavuconazole) with zinc and iron chelators (deferasirox and clioquinol respectively) along with alkalizer (glycine buffer) could be an effective and multi-target approach for the treatment of mucormycosis while being cost effective also.

Protein and peptide delivery to lungs by using advanced targeted drug delivery.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

A novel nano therapeutic using convalescent plasma derived exosomal (CPExo) for COVID-19: A combined hyperactive immune modulation and diagnostics.

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.

Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective.

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.

OUTBREAK of novel corona virus disease (COVID-19): Antecedence and aftermath.

Outbreak of Coronavirus disease 2019 (COVID-19) started in mid of December 2019 and spread very rapidly across the globe within a month of its outbreak. Researchers all across the globe started working to find out its possible treatments. However, most of initiatives taken were based on various hypotheses and till date no successful treatments have been achieved. Some strategies adopted by China where existing antiviral therapy was initially used to treat COVID-19 have not given very successful results. Researchers from Thailand explored the use of combination of anti-influenza drugs such as Oseltamivir, Lopinavir and Ritonavir to treat it. In some cases, combination therapy of antiviral drugs with chloroquine showed better action against COVID-19. Some of the clinical studies showed very good effect of chloroquine and hydroxychloroquine against COVID-19, however, they were not recommended due to serious clinical toxicity. In some cases, use of rho kinase inhibitor, fasudil was found very effective. In some of the countries, antibody-based therapies have proved fairly successful. The use of BCG vaccines came in light; however, they were not found successful due to lack of full-proof mechanistic studies. In Israel as well as in other developed countries, pluristems allogeneic placental expanded cell therapy has been found successful. Some phytochemicals and nutraceuticals have also been explored to treat it. In a recent report, the use of dexamethasone was found very effective in patients suffering from COVID-19. Its effect was most striking among patients on ventilator. The research for vaccines that can prevent the disease is still going on. In light of the dynamic trends, present review focuses on etiopathogenesis, factors associated with spreading of the virus, and possible strategies to treat this deadly infection. In addition, it attempts to compile the recent updates on development of drugs and vaccines for the dreaded disease.