Antiviral Discovery for Highly Pathogenic Emerging Viruses
Published:26 Nov 2021
Special Collection: 2021 ebook collectionSeries: Drug Discovery
2021. "Preface", Antiviral Discovery for Highly Pathogenic Emerging Viruses, César Muñoz-Fontela, Rafael Delgado
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Environmental threats such as climate change, deforestation and the consequences of globalization such as increase in air travel are major drivers of emergence of new infectious diseases, in particular those caused by viruses. Recent outbreaks have been caused by viruses with an extraordinary virulence such as Ebola virus, Middle-East respiratory syndrome (MERS) coronavirus (CoV), Nipah, Lassa, Hantaviruses or Crimean-Congo Hemorrhagic fever virus, or with great epidemiological impact such as Zika virus and severe acute respiratory syndrome (SARS)-CoV-2. All these highly pathogenic viruses are zoonotic and usually emerge in human populations with no pre-existing antibody immunity. This, and the fact that there are no clinically proven vaccines against these infections, underscore the need to develop vaccines as well as new antivirals and post-exposure treatments.
This collection illustrates how differences in virus tropism, receptor use and immune antagonism pose a tremendous challenge for the development of therapeutic countermeasures against emerging viruses. Despite these caveats, control of widely disseminated pathogenic viruses such as smallpox, measles or polio has been achieved in the past by the use of vaccines whose contribution to global health during the last two centuries has been prodigious. Moreover, in the last two decades, the development of antiviral strategies for agents such as the Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) has achieved outstanding results in the control of viral diseases for which vaccination turned out to be particularly difficult. A detailed knowledge of the structure and mechanism of action of key viral enzymes such as proteases, polymerases or integrases, along with the implementation of high throughput functional assays has resulted in targeted screening approaches and iterative synthetic optimization of potent inhibitors of viral replication. Despite these important stories of success, the therapeutic arsenal for most emerging viruses is quite limited. Indeed, until the global alarm caused by the West Africa EVD epidemic of 2013–2016, research on medical countermeasures for emerging viruses had received only moderate attention.
Recently, in particular since the emergence of COVID-19, global awareness of the threat posed by zoonotic viruses has increased dramatically. This has resulted in a significant increase in public interest, which translated into funding for surveillance, preparedness, rapid detection and also research in therapeutics. A number of biosafety level 3 and level 4 (BSL3, BSL4) facilities have been activated or expanded, and experimental animal models of infection have been optimized and extensively used for the development of vaccines and new antiviral drugs. Thus, the virology and immunology of emergent viruses have rapidly evolved into very active research fields. This, in turn, has prompted the application of new technologies such as high throughput screening, metagenomics, systems biology, isolation and characterization of monoclonal antibodies and reverse vaccinology to the development of vaccines and therapeutics against emerging viruses.
EVD in Africa and COVID-19 have also provided new opportunities to implement randomized controlled clinical trials (RCT) in the midst of epidemics and results of clinical efficacy of a number of antiviral strategies and vaccines have been obtained.
Historically, the development of vaccines against emerging viral infections has been hampered by the unpredictability of outbreaks. For example, it is not possible to predict where the next EVD or Nipah infection outbreak will occur, thereby precluding preventive vaccination campaigns. In addition, the paucity of human patients of these diseases has also limited the possibility of clinical trials, and the relatively small number of cases compared to other prominent diseases, has diminished the interest of pharmaceutical companies in vaccine development. This status quo has been drastically changed by the COVID-19 pandemic, which has seen the largest and fastest development of vaccines against a pathogen in the history of mankind. At the time of writing, four vaccines against COVID-19 have been approved and more than 70 are already in clinical trials. With the world facing the emergence of SARS-CoV-2 variants and vaccine inequity, it will be exciting to learn how we benefit from this experience and, hopefully, initiate a post-COVID era with enhanced surveillance and preparedness for future emergence of zoonotic viruses.
A broad scope of antiviral strategies has been adopted and we will cover the different progress in vaccines, antibodies and small molecular drugs that have taken place in the field. The volume was conceived as a state-of-the-art compilation of therapeutics for highly pathogenic agents that could be valuable for a broad spectrum of specialists, from medicinal chemistry to virologists and clinicians, but also as an introductory tool for undergraduates and early-stage researchers in this exciting field. To this end, we present pathogen-dedicated chapters prepared by the leading groups in their field. We thank the Royal Society of Chemistry for the kind and timely invitation to edit this volume and the collaboration of all the authors in writing and updating chapters in a setting of continued developments between 2018 and 2021.
César Muñoz-Fontela, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Rafael Delgado, Instituto de Investigación Hospital Universitario, Universidad Complutense School of Medicine, Madrid, Spain.