Biologics, Volume 1, Issue 3 (December 2021) – 8 articles

The ongoing pandemic situation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global threat to both the world economy and public health. Therefore, there is an urgent need to discover effective vaccines or drugs to fight against this virus. The flavonoids and their medicinal plant sources have already exhibited various biological effects, including antiviral, anti-inflammatory, antioxidant, etc. This study was designed to evaluate different flavonoids from medicinal plants as potential inhibitors against the spike protein (Sp) and main protease (M^pro) of SARS-CoV-2 using various computational approaches such as molecular docking, molecular dynamics. The binding affinity and inhibitory effects of all studied flavonoids were discussed and compared with some antiviral drugs that are currently being used in COVID-19 treatment namely favipiravir, lopinavir, and hydroxychloroquine, respectively. Among all studies flavonoids and proposed antiviral drugs, luteolin and mundulinol exhibited the highest binding affinity toward Mpro and Sp. Drug-likeness and ADMET studies revealed that the chosen flavonoids are safe and non-toxic. One hundred ns-MD simulations were implemented for luteolin-Mpro, mundulinol-Mpro, luteolin-Sp, and mundulinol-Sp complexes and the results revealed strong stability of these flavonoid-protein complexes. Furthermore, MM/PBSA confirms the stability of luteolin and mundulinol interactions within the active sites of this protein. In conclusion, our findings reveal that the promising activity of luteolin and mundulinol as inhibitors against COVID-19 via inhibiting the spike protein and major protease of SARS CoV-2, and we urge further research to achieve the clinical significance of our proposed molecular-based efficacy. Full article

Ingesting probiotics contributes to the development of a healthy microflora in the GIT with established benefits to human health. Some of these beneficial effects may be through the modulation of the immune system. In addition, probiotics have become more common in the treatment of many inflammatory and immune disorders. Here, we demonstrate a range of immune modulating effects of Streptococcus thermophilus by human monocytes, including decreased mRNA expression of IL-1R, IL-18, IFNαR1, IFNγR1, CCL2, CCR5, TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-8, CD14, CD86, CD4, ITGAM, LYZ, TYK2, IFNR1, IRAK-1, NOD2, MYD88, SLC11A1, and increased expression of IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-23, IFNγ, TNFα, CSF-2. The routine administration of Streptococcus thermophilus in fermented dairy products and their consumption may be beneficial to the treatment/management of inflammatory and autoimmune diseases. Full article

The calcium ion (Ca²⁺) plays a fundamental role in the metabolism and cell physiology of eukaryotic cells. In general, increases in cytosolic Ca²⁺ may come from both of the extracellular environment through specific channels and/or calcium release from intracellular stores. The mechanism by which the ion calcium (Ca²⁺) is released from intracellular stores in higher eukaryotes is well known; however, in lower eukaryotes is still a subject of study. In the present work, it was elucidated that Trypanosoma cruzi epimastigotes can release Ca²⁺ from intracellular stores in response to high osmolarity, in a process involving a protein kinase-regulated Na⁺/H⁺ exchanger present in the acidocalsisomes of the parasite. In addition, we demonstrated that epimastigote membranes are able to release Ca²⁺ in response to exogenous activators of both inositol 1,4,5-triphosphate (IP₃) and Ryanodine receptors. Furthermore, we also summarize the involvement of calcium-related signaling pathways in biochemical and morphological changes triggered by hyperosmotic stress in T. cruzi epimastigotes. Full article

The coronavirus disease 2019 (COVID-19), a life-threatening pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in massive destruction and is still continuously adding to its death toll. The advent of this global outbreak has not yet been confirmed; however, investigation for suitable prophylaxis against this lethal virus is being carried out by experts all around the globe. The SARS-CoV-2 belongs to the Coronaviridae superfamily, like the other previously occurring human coronavirus variants. To better understand a new virus variant, such as the SARS-CoV-2 delta variant, it is vital to investigate previous virus strains, including their genomic composition and functionality. Our study aimed at addressing the basic overview of the virus’ profile that may provide the scientific community with evidence-based insights into COVID-19. Therefore, this study accomplished a comprehensive literature review that includes the virus’ origin, classification, structure, life cycle, genome, mutation, epidemiology, and subsequent essential factors associated with host–virus interaction. Moreover, we summarized the considerable diagnostic measures, treatment options, including multiple therapeutic approaches, and prevention, as well as future directions that may reduce the impact and misery caused by this devastating pandemic. The observations and data provided here have been screened and accumulated through extensive literature study, hence this study will help the scientific community properly understand this new virus and provide further leads for therapeutic interventions. Full article

Coronavirus disease, COVID-19, has touched every country globally except five countries (North Korea, Turkmenistan, Tonga, Tuvalu and Nauru). Vaccination is the most effective method to protect against infectious diseases. The objective is to ensure that everyone has access to a COVID-19 vaccine. The conventional vaccine development platforms are complex and time-consuming to obtain desired approved vaccine candidates through rigorous regulatory pathways. These safeguards guarantee that the optimized vaccine product is safe and efficacious for various demographic populations prior to it being approved for general use. Nucleic acid vaccines employ genetic material from a pathogen, such as a virus or bacteria, to induce an immune response against it. Based on the vaccination, the genetic material might be DNA or RNA; as such, it offers instructions for producing a specific pathogen protein that the immune system will perceive as foreign and mount an immune response. Nucleic acid vaccines for multiple antigens might be made in the same facility, lowering costs even more. Most traditional vaccine regimens do not allow for this. Herein, we demonstrate the recent understanding and advances in nucleic acid vaccines (DNA and mRNA based) against COVID-19, specifically those in human clinical trials. Full article

Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be necessary to avoid inappropriate treatment strategies. Hence, the search for other alternative strategies as effective biofilm treatment options has become a growing area of research. The current review aims to give an overview of the mechanisms governing biofilm formation and the different strategies employed so far in the control of biofilm infections caused by P. aeruginosa. Moreover, this review can also help researchers to search for new antibiofilm agents to tackle the effect of biofilm infections that are currently imprudent to conventional antibiotics. Full article

Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview. Full article

High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed. Full article