Current Protein and Peptide Science - Volume 22, Issue 4, 2021

Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and responds with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARSCoV- 2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

Tuberculosis (TB) remains a serious threat to whole human health. In particular, the drug resistance of Mycobacterium tuberculosis (Mtb) has become a huge challenge in clinical medicine, and it is extremely urgent to develop effective inhibitors with novel structures and mechanisms. Belonging to the Resistance, Nodulation and Division (RND) superfamily, Mycobacterial membrane proteins Large 3 (MmpL3) is mainly responsible for transporting mycolic acid outside cell membrane to form cell wall, and plays critical roles in iron acquisition which is vital to the survival of Mtb. As a potential Mtb target in recent years, its inhibitor research has attracted wide attention. A series of inhibitors (such as SQ109, AU1235, BM212, etc.) through experimental screening have been reported in succession, especially SQ109 has entered the clinical stage. In this paper, the structural biology information of target MmpL3 was summarized, and the structure-activity relationship (SAR) of inhibitors reported in recent years and their inhibitory mechanism both were reviewed, aiming to provide help for the rational design of MmpL3 inhibitors in the future.

Enzymes are the biocatalysts synthesized by living organisms having high specificity, catalytic activity, and a broad range of applicability. One such biotechnologically relevant enzyme is keratinase with various industrial applications that capture a significant place in the enzyme market. It belongs to the proteolytic enzyme group that cleaves the highly stable and fibrous protein, keratin through hydrolysis. Keratins are hard-degrading fibrous proteins insoluble in natural solvents and water. It is frequently aggregated in nature and expressively present in the plumes, hair, nail, horn, skins, feet, etc. The broad range of microorganisms, such as bacteria, fungi, and actinomycetes, have been accounted for producing keratinases with significant biotechnological applications. Successful application of this group of enzymes has been seen in various industries such as farming, laundry detergent, cosmetics, animal feed, pharmaceutical, leather, and textile. Moreover, they have found remarkable usability in environment friendly waste management also. This paper focuses on the structure, sources, and various applications of this industrially important enzyme.

Polyphenol is an intricate bioactive molecule abundant in humans/animals’ diet particularly plant foods, and has been evidenced in numerous reports with health-promoting functions, owing to its free radical scavenging properties and a broad spectrum of bioactivities. However, the beneficial functions are linked and restricted to bioavailability, which is dictated by the diversity of the gut microbiota. The human/animal’s gut harbours a complex community of trillions of microbial species and their symbiotic relationship goes beyond mere aiding the host’s digestive system, with important functions such as host nutrition and health by encouraging nutrient metabolism and absorption, regulation of the gastrointestinal development, protection against pathogens, maintenance of the gut mucosal barrier functions and host immune system. The disruption of the gut community (i.e., dysbiosis) is suggested to reflect several pathological processes, such as diabetes, obesity, and other metabolic-related comorbidities. Recent improvements in deep-sequencing technologies and bioinformatics have enabled a more complex understanding of the reciprocal interactions of dietary polyphenols and gut microbiota, as well as their metabolic impact. Hence this review seeks to discuss the two-way synergistic interactions of dietary polyphenols and dietary constituents on the gut microbial composition with an updated and pivotal finding from literature suggesting whether these interactions depict a positive, negative, or neutralizing effect in the prevention of metabolic diseases.

The eukaryotic translation initiation factor 4E (eIF4E) is dysregulated in a wide variety of cancers. Higher expression of eIF4E promotes tumorigenesis and has been implicated in cancer development and progression. Regulation of eIF4E is particularly controlled through phosphorylation yielding phospho-eIF4E (p-eIF4E). p-eIF4E is a signaling molecule that participates in several pathways, including regulating various cancer-related processes. The role of phosphorylation of eIF4E at Serine 209 on oncogenic transformation has been appreciated for the last 10 years and has been under active investigation as a therapeutic target for cancers including acute myeloid leukemia (AML), but the expression of p-eIF4E in the nucleus and the specific molecular mechanism of action remain largely unresolved. It is selectively and highly expressed in AML where its expression was associated with poor outcomes and prognosis. The purpose of this review is to describe p-eIF4E as an indicator prognosis and a potential anticancer target for biological therapy of AML.

Microbial resistance to conventional therapeutics has become a significant threat to human society. Biofilms serve as the major virulence factor for the microorganisms by resisting the antibiotics and host innate immune system. Antimicrobial peptides (AMPs) have emerged as a potential alternative to conventional therapeutics due to their exceptional anti-biofilm and broad-spectrum antimicrobial property. Researchers have applied bioinformatics, genetic engineering, tissue culture, and drug delivery approaches to enhance the production and therapeutic efficacy of antimicrobial peptides. This review comprehensively describes the various aspects of AMPs with particular focus on their anti-biofilm potential. Other detailed information highlighted in this review includes different classes of AMPs, their mode of action, and anti-biofilm activity both alone and in synergy with other AMPs or conventional antibiotics. Further, challenges and opportunities of AMPs based drug delivery systems such as nano-formulations, polymeric micelles, and vesicles are also summarized.