ABSTRACT
Secretory proteins are playing important role during the host-pathogen interaction to develop the infection or protection into the cell. Pathogens developing infectious disease to human being are taken up by host macrophages or number of immune cells, play an important role in physiological, developmental and immunological function. At the same time, infectious agents are also secreting various proteins to neutralize the resistance caused by host cells and also helping the pathogens to develop the infection. Secretory proteins (secretome) are only developed at the time of host-pathogen interaction, therefore they become very important to develop the targeted and potential therapeutic strategies. Pathogen specific secretory proteins released during interaction with host cell provide opportunity to develop point of care and rapid diagnostic kits. Proteins secreted by pathogens at the time of interaction with host cell have also been found as immunogenic in nature and numbers of vaccines have been developed to control the spread of human infectious diseases. This chapter highlights the importance of secretory proteins in the development of diagnostic and therapeutic strategies to fight against human infectious diseases.
Subject(s)
Communicable Diseases , Vaccines , Humans , Host-Pathogen Interactions , Macrophages , Communicable Diseases/diagnosis , Communicable Diseases/therapyABSTRACT
SARS-CoV-2 and its variants cause serious health concerns throughout the world. The alarming increase in the daily number of cases has become a nightmare in many low-income countries; although some vaccines are available, their high cost and low vaccine production make them unreachable to ordinary people in developing countries. Other treatment strategies are required for novel therapeutic options. The peptide-based drug is one of the alternatives with low toxicity, more specificity, and ease of synthesis. Herein, we have applied structure-based virtual screening to identify potential peptides targeting the critical proteins of SARS-CoV-2. Non-toxic natural antiviral peptides were selected from the enormous number of peptides. Comparative modeling was applied to prepare a 3D structure of selected peptides. 3D models of the peptides were docked using the ClusPro docking server to determine their binding affinity and peptide-protein interaction. The high-scoring peptides were docked with other crucial proteins to analyze multiple targeting peptides. The two best peptides were subjected to MD simulations to validate the structure stability and evaluated RMSD, RMSF, Rg, SASA, and H-bonding from the trajectory analysis of 100 ns. The proposed lead peptides can be used as a broad-spectrum drug and potentially develop as a therapeutic to combat SARS-CoV-2, positively impacting the current pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02113-9.
ABSTRACT
COVID-19 is a highly transmissible disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects 226 countries and continents, and has resulted in >6.2 million deaths worldwide. Despite the efforts of all scientific institutions worldwide to identify potential therapeutics, no specific drug has been approved by the FDA to treat the COVID-19 patient. SARS-CoV-2 variants of concerns make the potential of publicly known therapeutics to respond to and detect disease onset highly improbable. The quest for universal therapeutics pointed to the ability of RNA-based molecules to shield and detect the adverse effects of the COVID-19 illness. One such candidate, miRNA (microRNA), works on regulating the differential expression of the target gene post-transcriptionally. The prime focus of this review is to report the critical miRNA molecule and their regular expression in patients with COVID-19 infection and associated comorbidities. Viral and host miRNAs control the etiology of COVID-19 infection throughout the life cycle and host inflammatory response, where host miRNAs are identified as a double-edged showing as a proviral and antiviral response. The review also covered the role of viral miRNAs in mediating host cell signaling expression during disease pathology. Studying molecular interactions between the host and the SARS-CoV-2 virus during COVID-19 pathogenesis offers the chance to use miRNA-based therapeutics to reduce the severity of the illness. By utilizing an appropriate delivery vehicle, these small non-coding RNA could be envisioned as a promising biomarker in designing a practical RNAi-based treatment approach of clinical significance.