Assessment of the efficacy of SARS-CoV-2 vaccines in non-human primate studies: a systematic review

Background: The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the rapid and successful development of vaccines to help mitigate the effect of COVID-19 and circulation of the virus. Vaccine efficacy is often defined as capacity of vaccines to prevent (severe) disease. However, the efficacy to prevent transmission or infectiousness is equally important at a population level. This is not routinely assessed in clinical trials. Preclinical vaccine trials provide a wealth of information about the presence and persistence of viruses in different anatomical sites. Methods: We systematically reviewed all available preclinical SARS-CoV-2 candidate vaccine studies where non-human primates were challenged after vaccination (PROSPERO registration: CRD42021231199). We extracted the underlying data, and recalculated the reduction in viral shedding. We summarized the efficacy of vaccines to reduce viral RNA shedding after challenge by standardizing and stratifying the results by different anatomical sites and diagnostic methods. We considered shedding of viral RNA as a proxy measure for infectiousness. Results: We found a marked heterogeneity between the studies in the experimental design and the assessment of the outcomes. The best performing vaccine candidate per study caused only low (6 out of 12 studies), or moderate (5 out of 12) reduction of viral genomic RNA, and low (5 out of 11 studies) or moderate (3 out of 11 studies) reduction of subgenomic RNA in the upper respiratory tract, as assessed with nasal samples. Conclusions: Since most of the tested vaccines only triggered a low or moderate reduction of viral RNA in the upper respiratory tract, we need to consider that most SARS-CoV-2 vaccines that protect against disease might not fully protect against infectiousness and vaccinated individuals might still contribute to SARS-CoV-2 transmission. Careful assessment of secondary attack rates from vaccinated individuals is warranted. Standardization in design and reporting of preclinical trials is necessary.

The Study of Traditional Medicine for the Treatment of COVID-19

SARS-CoV-2 is a novel virus communicable disease affected by serious acute respiratory condition coronavirus 2 (SARS-CoV-2) which goes to the family of coronavirus. December 2019, in Wuhan, China, the first case of novel coronavirus was reported, and this widespread virus globally became a pandemic. Various studies show that drug applicants are used as antivirals or immune modulators. Yet, the outcome of this examination reported the drug applicants were not ominously operative in contrast to the infection. In the interim, it's believed that taking herbal immune-modulators can avoid and/or resist COVID-19. Unluckily, definite clinical and preclinical trials to assess the special herbal immune regulators' effects have not been directed. Specific natural elements might be actual for treating COVID-19 built on universal thoughts from former tests. Though there are no exact anti-COVID-19 medicines as well as a drugs until now, the use of traditional medicine and epidemiology of novel coronavirus disease will be discussed for COVID-19 treatment.

Crude Extract of Terminalia Chebula Fruit Effect on Gastro Intestinal Disorders Using Different Animal Models

Terminalia chebula is an ancient medicinal herb. it is also known as Haritaki, Yellow myrobalan, Chebulic myrobalan, Yellow myrobalan, and Terminalia chebulabe longs to Combretaceae family is a major Ayurvedic medicine that is native to South Asia, predominantly from India. Apart from Ayurveda, it is commonly used in Unani and Homeopathic medicine systems. Because of the broad variety of pharmacological activities connected with the biologically active constitutents found throughout this herb, it is included in conventional medicine. The fruit contains main pharmacological activities such as Hepatoprotective activity, Cytoprotective activity Cardioprotective activity, Antidiabetic and renoprotective activity, Antibacterial activity, Antifungal activity, Antiviral activity, Antiprotozoal activity, Anti-inflammatory and anti-arthritic activity, antioxidant and free radical scavenging activity, Anticarcinogenic activity, Antimutagenic, radioprotective and Chemopreventive activity, Hypolipidemic and hypocholesterolemic activity, Adaptogenic and anti anaphylactic activities, Gastrointestinal motility improving and anti-ulcerogenic activity, Antispasmodic activity, Wound healing activity, Anticaries activity, Immunomodulatory activity any many are reported with scientific evidence. All these ancient applications of Terminalia chebula as home remedies have been confirmed in preclinical trials. The current evidence on the effect of Terminalia chebula intake or consumption on gastrointestinal disorders and diseases is scientifically based on preclinical and clinical trials. All these ancient applications of Terminalia chebula as home remedies have been confirmed in preclinical trials. The current evidence on the effect of Terminalia chebula intake or consumption on gastrointestinal disorders and diseases is scientifically based on preclinical and clinical trials. Study indicates different dosage of Terminalia chebula is effective to get relief from gastrointestinal troubles. Due to less number of gastrointestinal studies, there is no scientific report to consume a specific amount of dose. To prove that Terminalia chebula and its standard extracts are effective as a gastroprotective agent, more comprehensive preclinical and clinical trials are required. To reliably evaluate the appropriate dosages for specific disorders and preparation of extract of Terminalia chebula fruit in prospective human trials procedures, dose-finding preclinical studies should be conducted. There is an evident need for more patient and physician education concerning specific therapies, legislation to regulate the quality of pharmaceutical preparations, and, in particular, more clinical and pre-clinical trials to determine the value and safety of such medicaments in digestive and other disorders.

The Effectiveness and Safety of Probiotic Supplements for Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Preclinical Trials

Background. Patients with psoriasis need long-term medication to control their condition. Recent studies suggest that changing the intestinal flora may be a potential treatment. Methods. The databases were utilized to search the randomized controlled trials (RCTs) and preclinical trials about probiotic supplement in the treatment of psoriasis. The retrieval time is from the establishment of these databases to December 2020. RevMan5.3 was used for the risk assessment of bias and meta-analysis. This systematic review was registered in PROSPERO (CRD42021232756). Results. A total of 3 RCTs involving 164 participants were included. Two RCTs showed that probiotics can improve PASI and thereby improve the condition. For inflammation-related indicators, only one RCT showed that probiotics can improve the levels of CRP and TNF-α but have no obvious improvement effect on IL6. One RCT demonstrated the total effective rate of probiotics in the treatment of psoriasis. For adverse events, one RCT showed that the incidence of adverse events of probiotic treatment was low. Preclinical studies showed that continuous intervention with oral probiotics can significantly improve the progression of psoriasis and reduce the expression of inflammatory factors. The meta-analysis showed that the PASI between two groups was of no statistical significance (SMD 1.83 [-0.41, 4.07], P = 0.11 ). Meanwhile, probiotics may improve skin thickness (SMD -5.87 [-11.34, -0.41], P = 0.04 ) in animal model. Conclusion. Prebiotics may have a positive effect on alleviating the clinical symptoms of psoriasis, but a large sample of RCTs is still needed to support its therapeutic effect in psoriasis.

Artificial Intelligence (AI) in Drugs and Pharmaceuticals

: The advancement of computing and technology has invaded all the dimensions of science. Artificial intelligence (AI) is one core branch of Computer Science, which has percolated to all the arenas of science and technology, from core engineering to medicines. Thus, AI has found its way for application in the field of medicinal chemistry and heath care. The conventional methods of drug design have been replaced by computer-aided designs of drugs in recent times. AI is being used extensively to improve the design techniques and required time of the drugs. Additionally, the target proteins can be conveniently identified using AI, which enhances the success rate of the designed drug. The AI technology is used in each step of the drug designing procedure, which decreases the health hazards related to preclinical trials and also reduces the cost substantially. The AI is an effective tool for data mining based on the huge pharmacological data and machine learning process. Hence, AI has been used in de novo drug design, activity scoring, virtual screening and in silico evaluation in the properties (absorption, distribution, metabolism, excretion and toxicity) of a drug molecule. Various pharmaceutical companies have teamed up with AI companies for faster progress in the field of drug development, along with the healthcare system. The review covers various aspects of AI (Machine learning, Deep learning, Artificial neural networks) in drug design. It also provides a brief overview of the recent progress by the pharmaceutical companies in drug discovery by associating with different AI companies.

Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma

Proteasome substrate receptor hRpn13 is a promising anti-cancer target. By integrated in silico and biophysical screening, we identified a chemical scaffold that binds hRpn13 with non-covalent interactions that mimic the proteasome and a weak electrophile for Michael addition. hRpn13 Pru domain binds proteasomes and ubiquitin whereas its DEUBAD domain binds deubiquitinating enzyme UCHL5. NMR revealed lead compound XL5 to interdigitate into a hydrophobic pocket created by lateral movement of a Pru β-hairpin with an exposed end for Proteolysis Targeting Chimeras (PROTACs). Implementing XL5-PROTACs as chemical probes identified a DEUBAD-lacking hRpn13 species (hRpn13Pru) present naturally with cell type-dependent abundance. XL5-PROTACs preferentially target hRpn13Pru, causing its ubiquitination. Gene-editing and rescue experiments established hRpn13 requirement for XL5-PROTAC-triggered apoptosis. These data establish hRpn13 as an anti-cancer target for multiple myeloma and introduce an hRpn13-targeting scaffold that can be optimized for preclinical trials against hRpn13Pru-producing cancer types.

Role of the Microenvironment in Mesenchymal Stem Cell-Based Strategies for Treating Human Liver Diseases

Liver disease is a severe health problem that endangers human health worldwide. Mesenchymal stem cell (MSC) therapy is a novel treatment for patients with different liver diseases due to its vast expansion potential and distinctive immunomodulatory properties. Despite several preclinical trials having confirmed the considerable efficacy of MSC therapy in liver diseases, the questionable safety and efficacy still limit its application. As a precursor cell, MSCs can adjust their characteristics in response to the surrounding microenvironment. The microenvironment provides physical and chemical factors essential for stem cell survival, proliferation, and differentiation. However, the mechanisms are still not completely understood. We, therefore, summarized the mechanisms underlying the MSC immune response, especially the interaction between MSCs and the liver microenvironment, discussing how to achieve better therapeutic effects.

Diet, microbes, and cancer across the tree of life: a systematic review

Cancers are a leading cause of death in humans and for many other species. Diet has often been associated with cancers, and the microbiome is an essential mediator between diet and cancers. Here we review the work on cancer and the microbiome across species. We systematically reviewed over a thousand published articles and identified links between diet, microbes and cancers in several species of mammals, birds, and flies. Some microbes, specifically Fusobacteria, Bacteroides fragilis, Helicobacter bacteria, and papillomaviruses, have cancer-inducing effects in gerbils, mice, dogs, or cats. Other microbes, such as Lactobacillus species, mostly found in milk products, prevent gastrointestinal, breast, and lung cancers in mice and rats. Future work should examine a larger variety of host species to discover new model organisms for human preclinical trials, better understand the observed variance in cancer prevalence across species, and discover which microbes and diets are associated with cancers across species. Ultimately this could help identify microbial and dietary interventions to diagnose, prevent and treat cancers in humans as well as other animals.