Chapter 27 - Role of nutraceuticals as immunomodulators to combat viruses

Epidemics and pandemics have always been pulling down on human existence. Currently, we are facing the pandemic of COVID-19 caused by the SARS-CoV-2 virus. The existing treatment options for this virus affecting the respiratory tract fall short. Such viruses take advantage of their evolutionary benefit of evading the host immune responses to establish infection in the host. Thus, a patent immune system of the host is a must to tackle such infections. A vigilant immune system will identify the virus cells present in the host and try to contain the infection from spreading to other parts of the body by phagocytosing it with the help of specialized cells like macrophages, neutrophils, dendritic cells, etc. Antigen presenting cells present the viral peptides to the cytotoxic T cells to initiate the cascade of events leading to the formation of antibodies against the virus and clearing of the infection from the body. Viruses interfere with both the innate and adaptive immune responses to circumvent the host immunity. Evading the antigen presentation and molecular mimicry to subdue the cytokines are some of the mechanisms exhibited by viruses. Effective recuperation of health needs a “healthy” immune system and for this the most effective way is to utilize the plethora of chemical entities belonging to the nutraceuticals. Vast researches undergoing in the field of nutraceuticals adds sufficient evidence on their antiviral properties. This wisdom helps to use nutraceuticals as adjunctive therapies along with the conventional treatment regimes.

Chapter 18 - Herbal drugs to combat viruses

Mortality from emergent diseases escalated drastically with the 2019 pandemic of COVID-19. History hails the discovery of antibiotics as the key event that reduced death rate from infectious diseases. The myriads of antibiotics currently available saved the human race from becoming extinct to a large extent. Antibiotic resistance is the negative impact to improper use of antimicrobials. Resistant strains have created several epidemics specifically emanating from hospitals. Newer, stronger, and better antibiotics have replaced the ones to which organisms gained resistance. The genetic mechanism of resistance is now well understood. The cluster of genes, highly conserved through several species have provided the evolutionary advantage to the microbes to overcome antibiotic threats. This is true with bacteria and viruses alike. In case of viral infections, the scenario is entirely different as the effective antiviral agents are relatively newer. Resistance to antiviral agents is also reported widely in literature. Viruses, having the capability to mutate frequently, pose a newer threat to the treatment as many antiviral agents become ineffective. To make the conditions even worse, the emergence of newer viruses have created a new hurdle. Considering these facts, it is evident that conventional antiviral agents alone is sufficient to control viral infections. For this, ancillary help is solicited from other areas like boosting the immunity of the host and natural antiviral agents. Phytochemicals derived from medicinal plants and nutraceuticals provide ample opportunity to this notion and the current evidence available regarding their antiviral activity provides a promising hope.

Synthesis of novel coumarin analogues: Investigation of molecular docking interaction of SARS-CoV-2 proteins with natural and synthetic coumarin analogues and their pharmacokinetics studies.

The severe acute respiratory syndrome coronavirus, identified as SARS-CoV-2, initially established in Wuhan, China at the end of 2019, affects respiratory infections known as COVID-19. In an extraordinary manner, COVID-19 is affecting human life and has transformed a global public health issue into a crisis. Natural products are already recognized owing to the massive advantageous window and efficient antioxidant, antiviral immunomodulatory, and anti-inflammatory belongings. Additionally, the object of the present study was to demonstrate the inhibitory potential of the natural products coumarins and its analogues alongside SARS coronavirus. The present work, focuses on the synthesis of new coumarin analogues and characterized by FT-IR, 1H and 13C NMR, elemental analyses, and mass spectra. The recently synthesised compounds were projected conceptual association for COVID-19 protease and also to explore in anticipation if this protein will help target protease inhibitor drugs such as Calanolide A, Cardatolide A, Collinin, Inophyllum A, Mesuol, Isomesuol, Pteryxin, Rutamarin, Seselin and Suksdorin. The natural coumarin analogues docking scores were compared to standard Hydroxychloroquine. While the 3D module of SARS coronavirus main protease was predicted with the SWISS MODEL web server, as well as biochemical interaction tests were performed with the AutoDock Vina tool between the target protein with ligands. This research further showed that all the protease inhibitors accessed the target protein with negative dock energy. Molecular docking studies found that the natural coumarin analogue Inophyllum A showed an exceptional potential for inhibition with a binding energy of -8.4 kcal/mol. The synthetic coumarin analogues 1m and 1p both demonstrated a similar binding energy, inhibition potential of -7.9 kcal / mol as opposed to hydroxychloroquine and co-crystallized ligand alpha-ketoamide with binding energy values of -5.8 and -6.6 kcal / mol. All compounds evaluated were known as drug-like in nature, passing Lipinski's "Law of 5" with 0 violations except for alpha-ketoamide, passing Lipinski's "Rule of 5" with 1 violation (MW > 500). The inhibitor binding in silico research thus offers a structural understanding of COVID-19 and molecular interactions across the known protease inhibitors centred on the findings of the multiple sequence alliance.

Emerging paradigms of viral diseases and paramount role of natural resources as antiviral agents.

In the current scenario, the increasing prevalence of diverse microbial infections as well as emergence and re-emergence of viral epidemics with high morbidity and mortality rates are major public health threat. Despite the persistent production of antiviral drugs and vaccines in the global market, viruses still remain as one of the leading causes of deadly human diseases. Effective control of viral diseases, particularly Zika virus disease, Nipah virus disease, Severe acute respiratory syndrome, Coronavirus disease, Herpes simplex virus infection, Acquired immunodeficiency syndrome, and Ebola virus disease remain promising goal amidst the mutating viral strains. Current trends in the development of antiviral drugs focus solely on testing novel drugs or repurposing drugs against potential targets of the viruses. Compared to synthetic drugs, medicines from natural resources offer less side-effect to humans and are often cost-effective in the productivity approaches. This review intends not only to emphasize on the major viral disease outbreaks in the past few decades and but also explores the potentialities of natural substances as antiviral traits to combat viral pathogens. Here, we spotlighted a comprehensive overview of antiviral components present in varied natural sources, including plants, fungi, and microorganisms in order to identify potent antiviral agents for developing alternative therapy in future.