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      Antivirals: Past, Present and Future

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          Abstract

          The uses of antiviral agents are increasing in the new era along with the development of vaccines for the effective control of viral diseases. The main aims of antiviral agents are to minimize harm to the host system and eradicate deadly viral diseases. However, the replications of viruses in host system represent a massive therapeutic challenge than bacteria and fungi. Antiviral drugs not just penetrate to disrupt the virus’ cellular divisions but also have a negative impact on normal physiological pathways in the host. Due to these issues, antiviral agents have a narrow therapeutic index than antibacterial drugs. Nephrotoxicity is the main adverse reaction of antiviral drugs in human and animals. In this chapter, we summarize the antiviral agents’ past, present and future perspectives with the main focus on the brief history of antiviral in animals, miscellaneous drugs, natural products, herbal and repurposing drugs.

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          Antiviral actions of interferons.

          C Samuel (2001)
          Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.
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            Natural products to drugs: natural product-derived compounds in clinical trials.

            John S. Butler (2008)
            Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.
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              Importance of microbial natural products and the need to revitalize their discovery.

              Arnold Demain (2014)
              Microbes are the leading producers of useful natural products. Natural products from microbes and plants make excellent drugs. Significant portions of the microbial genomes are devoted to production of these useful secondary metabolites. A single microbe can make a number of secondary metabolites, as high as 50 compounds. The most useful products include antibiotics, anticancer agents, immunosuppressants, but products for many other applications, e.g., antivirals, anthelmintics, enzyme inhibitors, nutraceuticals, polymers, surfactants, bioherbicides, and vaccines have been commercialized. Unfortunately, due to the decrease in natural product discovery efforts, drug discovery has decreased in the past 20 years. The reasons include excessive costs for clinical trials, too short a window before the products become generics, difficulty in discovery of antibiotics against resistant organisms, and short treatment times by patients for products such as antibiotics. Despite these difficulties, technology to discover new drugs has advanced, e.g., combinatorial chemistry of natural product scaffolds, discoveries in biodiversity, genome mining, and systems biology. Of great help would be government extension of the time before products become generic.
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                Author and article information

                Contributors
                Yashpal Singh Malik: malikyps@ivri.res.in
                Raj Kumar Singh: rks_virology@rediffmail.com
                Mahendra Pal Yadav: yadav_mp@hotmail.com
                Kamal Niaz: kamalniaz1989@gmail.com
                Journal
                Journal ID (publisher-id): 978-981-13-9073-9
                Journal ID (doi): 10.1007/978-981-13-9073-9
                Journal ID (nlm-ta): Recent Advances in Animal Virology
                Title: Recent Advances in Animal Virology
                ISBN (Print): 978-981-13-9072-2
                ISBN (Electronic): 978-981-13-9073-9
                Publication date (Electronic): 6 June 2019
                Pages: 425-446
                Affiliations
                [1 ]GRID grid.417990.2, ISNI 0000 0000 9070 5290, ICAR-Indian Veterinary Research Institute (ICAR-IVRI), ; Izatnagar, Uttar Pradesh India
                [2 ]GRID grid.417990.2, ISNI 0000 0000 9070 5290, ICAR-Indian Veterinary Research Institute (ICAR-IVRI), ; Izatnagar, Uttar Pradesh India
                [3 ]GRID grid.444573.5, ICAR-Indian Veterinary Research Institute (ICAR-IVRI), Izatnagar, Uttar Pradesh, India, , Sardar Vallabhbhai Patel University of Agriculture and Technology, ; Meerut, India
                [4 ]GRID grid.427581.d, Department of Pharmacy, College of Medicine and Health Sciences, , Ambo University, ; Ambo, Ethiopia
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Toxicology and Pharmacology, The Institute of Pharmaceutical Sciences, , Tehran University of Medical Sciences, ; Tehran, Iran
                [6 ]GRID grid.412967.f, Department of Pharmacology and Toxicology, Faculty of Bio-Sciences, , Cholistan University of Veterinary and Animal Sciences (CUVAS), ; Bahawalpur, Pakistan
                Article
                Publisher ID: 22
                DOI: 10.1007/978-981-13-9073-9_22
                PMC ID: 7120554
                SO-VID: 5b388c5d-f8d2-4e49-9d09-8d6ac27526df
                Copyright © © Springer Nature Singapore Pte Ltd. 2019
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Subject: Article
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                issue-copyright-statement © Springer Nature Singapore Pte Ltd. 2019

                Keywords: virus,therapy,bacteria,dna,rna
                Data availability:
                Keywords: virus, therapy, bacteria, dna, rna

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