Future perspectives of emerging novel drug targets and immunotherapies to control drug addiction.

Substance Use Disorder (SUD) is one of the major mental illnesses that is terrifically intensifying worldwide. It is becoming overwhelming due to limited options for treatment. The complexity of addiction disorders is the main impediment to understanding the pathophysiology of the illness. Hence, unveiling the complexity of the brain through basic research, identification of novel signaling pathways, the discovery of new drug targets, and advancement in cutting-edge technologies will help control this disorder. Additionally, there is a great hope of controlling the SUDs through immunotherapeutic measures like therapeutic antibodies and vaccines. Vaccines have played a cardinal role in eliminating many diseases like polio, measles, and smallpox. Further, vaccines have controlled many diseases like cholera, dengue, diphtheria, Haemophilus influenza type b (Hib), human papillomavirus, influenza, Japanese encephalitis, etc. Recently, COVID-19 was controlled in many countries by vaccination. Currently, continuous effort is done to develop vaccines against nicotine, cocaine, morphine, methamphetamine, and heroin. Antibody therapy against SUDs is another important area where serious attention is required. Antibodies have contributed substantially against many serious diseases like diphtheria, rabies, Crohn's disease, asthma, rheumatoid arthritis, and bladder cancer. Antibody therapy is gaining immense momentum due to its success rate in cancer treatment. Furthermore, enormous advancement has been made in antibody therapy due to the generation of high-efficiency humanized antibodies with a long half-life. The advantage of antibody therapy is its instant outcome. This article's main highlight is discussing the drug targets of SUDs and their associated mechanisms. Importantly, we have also discussed the scope of prophylactic measures to eliminate drug dependence.

Association of SARS-CoV-2 and Polypharmacy with Gut-Lung Axis: From Pathogenesis to Treatment.

SARS-CoV-2 is a novel infectious contagion leading to COVID-19 disease. The virus has affected the lives of millions of people across the globe with a high mortality rate. It predominantly affects the lung (respiratory system), but it also affects other organs, including the cardiovascular, psychological, and gastrointestinal (GIT) systems. Moreover, elderly and comorbid patients with compromised organ functioning and pre-existing polypharmacy have worsened COVID-19-associated complications. Microbiota (MB) of the lung plays an important role in developing COVID-19. The extent of damage mainly depends on the predominance of opportunistic pathogens and, inversely, with the predominance of advantageous commensals. Changes in the gut MB are associated with a bidirectional shift in the interaction among the gut with a number of vital human organs, which leads to severe disease symptoms. This review focuses on dysbiosis in the gut-lung axis, COVID-19-induced worsening of comorbidities, and the influence of polypharmacy on MB.

Fiction and Facts about BCG Imparting Trained Immunity against COVID-19.

The Bacille Calmette-Guérin or BCG vaccine, the only vaccine available against Mycobacterium tuberculosis can induce a marked Th1 polarization of T-cells, characterized by the antigen-specific secretion of IFN-γ and enhanced antiviral response. A number of studies have supported the concept of protection by non-specific boosting of immunity by BCG and other microbes. BCG is a well-known example of a trained immunity inducer since it imparts 'non-specific heterologous' immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the recent pandemic. SARS-CoV-2 continues to inflict an unabated surge in morbidity and mortality around the world. There is an urgent need to devise and develop alternate strategies to bolster host immunity against the coronavirus disease of 2019 (COVID-19) and its continuously emerging variants. Several vaccines have been developed recently against COVID-19, but the data on their protective efficacy remains doubtful. Therefore, urgent strategies are required to enhance system immunity to adequately defend against newly emerging infections. The concept of trained immunity may play a cardinal role in protection against COVID-19. The ability of trained immunity-based vaccines is to promote heterologous immune responses beyond their specific antigens, which may notably help in defending against an emergency situation such as COVID-19 when the protective ability of vaccines is suspicious. A growing body of evidence points towards the beneficial non-specific boosting of immune responses by BCG or other microbes, which may protect against COVID-19. Clinical trials are underway to consider the efficacy of BCG vaccination against SARS-CoV-2 on healthcare workers and the elderly population. In this review, we will discuss the role of BCG in eliciting trained immunity and the possible limitations and challenges in controlling COVID-19 and future pandemics.

SARS-CoV-2 vaccines: Clinical endpoints and psychological perspectives: A literature review.

BACKGROUND: About 270 million cases have been confirmed, and 5.3 million fatalities Worldwide due to SARS-CoV-2. Several vaccine candidates have entered phase 3 of the clinical trial and are being investigated to provide immunity to the maximum percentage of people. A safe and effective vaccine is required to tackle the current COVID-19 waves. There have been reports that clinical endpoints and psychological parameters are necessary to consider vaccine efficacy. This review examines the clinical endpoints required for a successful SARS-CoV-2 vaccine and the influences of psychological parameters on its efficacy. METHODS: The main research question was to find out the clinical endpoints that determine the vaccine efficacy? And what kind of psychological parameters affect the vaccine efficacy? The information was taken from several journals, databases, and scientific search engines like Googe scholar, Pubmed, Scopus, Web of Science, Science direct, WHO website, and other various sites. The research studies were searched using keywords; SAR-CoV-2 vaccine efficacy, psychological effect on SARS-CoV-2 vaccine, SARS-CoV-2 vaccine endpoints. RESULTS: This review has highlighted various clinical endpoints that are the main determinants of clinical vaccine efficacy. Currently, vaccinations are being carried out throughout the world; it is important to investigate the main determinants affecting vaccine efficacy. We have focused on the clinical endpoints and the influence of psychological parameters that affect the vaccine efficacy in clinical settings. The primary endpoints include the risk of infection, symptoms, and severity of COVID-19, while hospitalization length, supplemental oxygen requirement, and mechanical ventilation are secondary endpoints in the clinical endpoints. Some tangential endpoints were also considered, including organ dysfunction, stroke, and MI. Many psychological associated things have influenced the vaccine efficacy, like the lower antibody titers in the vaccinated people. In addition to that, Short- and long-term stress and sleep deprivation were also found to affect the vaccine efficacy. CONCLUSION: The review summarizes the important clinical endpoints required for a successful vaccine candidate. In addition to primary and secondary endpoints, auxiliary endpoints and the disease burden also play an important role in modulating vaccine efficacy. Moreover, the psychological perspective also influences vaccine efficacy. Effective follow-up of participants should follow to examine the clinical endpoints to reach any conclusion about vaccine efficacy.

Clinical Characteristics and Treatment Outcomes of Mild to Moderate COVID-19 Patients at Tertiary Care Hospital, Al Baha, Saudi Arabia: A Single Centre Study.

OBJECTIVE: Since the severity of symptoms affects the treatment option for Coronavirus Disease 2019 (COVID-19) patients, the treatment pattern for mild to moderate non-ICU cases must be evaluated, particularly in the current scenario of mutation and variant strain for effective decision making. METHODS: The objective of retrospective analysis was to assess clinical and treatment outcomes in mild to moderate symptoms in non-ICU patients with COVID-19 who were admitted to major tertiary care hospitals in Al Baha, Saudi Arabia, between April and August 2020. RESULTS: A total of 811 people were admitted for COVID-19 treatment, age ranging from 14 to 66, diabetes mellitus (31%, n = 248) and hypertension (24%, n = 198) were the most common comorbid conditions. The hydroxychloroquine (HCQ) treated group (G1 n = 466) had an MD of 8 and an IQR of 5-13 for time in hospital with a 4.3% mortality rate, while the non-HCQ group (G2 n = 345) had an MD of 6 and an IQR of 3-11 for time in hospital with a 3.2% mortality rate. A combination of antiviral and antibiotic treatment was found to be effective, other most frequent intervention was analgesics 85.7%, anticoagulant 75%, minerals (Zinc 83% and Vit D3 82%). CONCLUSIONS: The therapy and clinical outcomes from the past will be the guiding factor to treat the COVID variants infection in the future. Patients treated with HCQ had a higher mortality rate, whereas those who were given a non-HCQ combination had a greater clinical outcome profile. DATA AVAILABILITY: Data available on request due to ethical restrictions. The anonymized data presented in this study are available on request from the corresponding author. The data are not publicly available to maintain privacy and adhere to guidelines of the ethics protocol.

The SARS-CoV-2 mutations versus vaccine effectiveness: New opportunities to new challenges.

BACKGROUND: The SARS-CoV-2 coronavirus epidemic is hastening the discovery of the most efficient vaccines. The development of cost-effective vaccines seems to be the only solution to terminate this pandemic. However, the vaccines' effectiveness has been questioned due to recurrent mutations in the SARS-CoV-2 genome. Most of the mutations are associated with the spike protein, a vital target for several marketed vaccines. Many countries were highly affected by the 2nd wave of the SARS-CoV-2, like the UK, India, Brazil and France. Experts are also alarming the further COVID-19 wave with the emergence of Omicron, which is highly affecting the South African populations. This review encompasses the detailed description of all vaccine candidates and COVID-19 mutants that will add value to design further studies to combat the COVID-19 pandemic. METHODS: The information was generated using various search engines like google scholar, PubMed, clinicaltrial.gov.in, WHO database, ScienceDirect, and news portals by using keywords SARS-CoV-2 mutants, COVID-19 vaccines, efficacy of SARS-CoV-2 vaccines, COVID-19 waves. RESULTS: This review has highlighted the evolution of SARS-CoV-2 variants and the vaccine efficacy. Currently, various vaccine candidates are undergoing several phases of development. Their efficacy still needs to check for newly emerged variants. We have focused on the evolution, multiple mutants, waves of the SARS-CoV-2, and different marketed vaccines undergoing various clinical trials and the design of the trials to determine vaccine efficacy. CONCLUSION: Various mutants of SARS-CoV-2 arrived, mainly concerned with the spike protein, a key component to design the vaccine candidates. Various vaccines are undergoing clinical trial and show impressive results, but their efficacy still needs to be checked in different SARS-CoV-2 mutants. We discussed all mutants of SARS-CoV-2 and the vaccine's efficacy against them. The safety concern of these vaccines is also discussed. It is important to understand how coronavirus gets mutated to design better new vaccines, providing long-term protection and neutralizing broad mutant variants. A proper study approach also needs to be considered while designing the vaccine efficacy trials, which further improved the study outcomes. Taking preventive measures to protect from the virus is also equally important, like vaccine development.

An overview of SARS-COV-2 epidemiology, mutant variants, vaccines, and management strategies.

BACKGROUND: Over the last two decades, humanity has observed the extraordinary anomaly caused by novel, weird coronavirus strains, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). As the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has made its entry into the world, it has dramatically affected life in every domain by continuously producing new variants. The vaccine development is an ongoing process, although some vaccines got marketed. The big challenge is now whether the vaccine candidates can provide long-lasting protection or prevention against mutant variants. METHODS: The information was gathered from various journals, electronic searches via Internet-based information such as PubMed, Google Scholar, Science Direct, online electronic journals, WHO landscape, world meters, WHO website, and News. RESULTS: This review will present and discuss some coronavirus disease 19 (COVID-19) related aspects including: the pathophysiology, epidemiology, mutant variants vaccine candidates, vaccine efficacy, and management strategies. Due to the high death rate, continuous spread, an inadequate workforce, lack of required therapeutics, and incomplete understanding of the viral strain, it becomes crucial to build the knowledge of its biological characteristics and make available the rapid diagnostic and vital therapeutic machinery for the combat and management of an infection. CONCLUSION: The data summarizes current research on the COVID 19 infection and therapeutic interventions, which will direct future decision-making on the effort-worthy phases of the COVID 19 and the development of critical therapeutics. The only possible solution is the vaccine development targeting against all variant strains to halt its progress; the identified theoretical and practical knowledge can eliminate the gaps to improve a better understanding of the novel coronavirus structure and its design of a vaccine. In addition, to that the long-lasting protection is another challenging objective that need to be looked into.

Targets and strategies for vaccine development against SARS-CoV-2.

The SARS-CoV-2, previously called a novel coronavirus, that broke out in the Wuhan city of China caused a significant number of morbidity and mortality in the world. It is spreading at peak levels since the first case reported and the need for vaccines is in immense demand globally. Numerous treatment and vaccination strategies that were previously employed for other pathogens including coronaviruses are now being been adopted to guide the formulation of new SARS-CoV-2 vaccines. Several vaccine targets can be utilized for the development of the SARS-CoV-2 vaccine. In this review, we highlighted the potential of various antigenic targets and other modes for formulating an effective vaccine against SARS-CoV-2. There are a varying number of challenges encountered during developing the most effective vaccines, and measures for tackling such challenges will assist in fast pace development of vaccines. This review will give a concise overview of various aspects of the vaccine development process against SARS-CoV-2, including 1) potential antigen targets 2) different vaccination strategies from conventional to novel platforms, 3) ongoing clinical trials, 4) varying challenges encountered during developing the most effective vaccine and the futuristic approaches.