Pharmaceuticals for Targeting Coronaviruses

Viral diseases have caused millions of deaths around the world. In the past, health organizations and pharmaceutical industries have neglected these diseases for years, mainly because they affected a small geographic population. In contrast, since 2016, several viral outbreaks have been reported worldwide, such as those caused by Ebola, Zika, and SARS-CoV2 (COVID-19). Thus, these have received more attention, leading to increased efforts to search for new antiviral drugs. The SARS-CoV-2 pandemic, already responsible for more than 1,254,567 deaths worldwide, is the greatest example of a virus that has always been present in our society, responsible for small outbreaks in Asian and Arabic countries in 2004 and 2012. But, investments in research to identify/discover new drugs and vaccines were only intensified in 2020, in which only the remdesivir (an FDA-approved drug) was developed to addressCOVID19 until today. Nonetheless, it has been used in hospitals in the United States and Japan, in emergency cases. Indeed, it justifies greater investments in discovering new alternatives that could save thousands of people. In this context, improving drug discovery techniques is fundamental in searching for new therapies that could be selective and effective to combat SARS-CoV-2. Drug discovery approaches are based on ligands (Ligand-Based Drug Design - LBDD) or structures (Structure-Based Drug Discovery - SBDD). Concerning SBDD, it is the main and most evolved technique used for discovering new drugs. The application of SBDD techniques has improved the pharmacological arsenal against diverse diseases, which allowed the discovery of innovative treatments, such as inhibitors of HIV-1 proteases. In this chapter, main SBDD techniques (i.e. homology modeling; molecular dynamics and docking; de novo drug discovery; pharmacophore modeling; fragment-based drug discovery; and virtual high-throughput screenings) applied to discover new hit compounds SARS-CoV-2 (COVID-19) will be discussed in details.

Considering the significant worldwide threat of the Novel Corona Virus Disease 2019 (COVID-19), it is urgently needed to develop efficient prevention and treatment approaches in order to reduce the prevalence rate and mortality of the disease. Even though numerous experimental and clinical studies have been currently conducted for development of drug and vaccine througout the world, and some partially effective vaccines and chemical drugs have been developed against COVID19. Herbal and dietary plants, including fruits, vegetables, herbs, spices, cereals, and edible tubers/roots, can play a significant role in enhanging the immune system and how to increase our defense barriers against virus-related diseases. Accordingly, medicinal plants with a wide range of bioactive compounds, which exhibit remarkable antiviral activities, can be used as a preventive treatment and cure for COVID-19. In order to combat SARS-CoV-2, rockrose (Cistus spp.), lemon balm (Melissa officinalis L.), rosemary (Rosmarinus officinalis L.), licorice root (Glyrrhiza glabra L.), olive leaf (Olea europea L.), peppermint (Mentha piperita L.), basil (Ocimum bacilicum L.), sumac (Rhus coriaria L.) and different species of thyme (Origanum, Thymus and Thymbra) are important medicinal plants that exhibit valuable antiviral activities. Since medicinal and aromatic plants are a worldwide hot topic, the aim of the current review was to provide an overview of the development of plant-based anti-coronavirus agents to the researchers based on an extensive literature survey.

 SARS-coronavirus (SARS-CoV) originated in China from 2002 to 2003 and caused a global outbreak with 8098 cases and 774 confirmed deaths. More than 15 years later, in less than a year, the new coronavirus (2019-nCoV) has infected more than 44 million people and killed more than 1 million. The COVID-19 pandemic has brought serious consequences for several countries and a worldwide alert about coronaviruses. Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clinical manifestations of the lower respiratory tract that lead to severe lung damage and the spread of the virus to several other organs. Phylogenetic analyzes demonstrate that SARS-CoV-2 shares a 79% identity with SARS-CoV, and just as there was no effective treatment against SARS-CoV, it does not yet exist against SARS-CoV-2. However, researchers from all over the world are dedicating themselves to several studies in an attempt to find the best treatment and prevention against the coronavirus. Thus, this book chapter addresses the main characteristics of SARS, the main targets and drugs that have achieved excellent results in clinical trials.

The corona virus disease (COVID-19) was started in Wuhan, China, in late 2019. It is caused by a novel strain of severe acute respiratory syndrome corona viruses (SARS-CoV-2) that has become pandemic on March 11, 2020 and endangered the existence of human beings on the earth as the infection has been spreading in mass population day by day within a few months with a high killing rate. The COVID-19 pandemic has pushed the modern health care system of developing and developed countries to their limits for its effective management and control since the drug discovery process is a long journey and challenging task and there is no specific small molecule chemotherapeutics to combat this novel coronavirus. Hence, the existence of human life is a great challenge. Mother Nature has played an important role to combat many pandemics that arrived in past centuries in absence of modern medicines. Nature has been a source of many natural drugs derived from plants' secondary metabolites which may be used to combat COVID-19. Natural sourced traditional Indian and Chinese medicines alternative therapy should be prioritized in combination with modern medicines to combat COVID-19. With rising COVID-19 cases globally, it would be too difficult to provide proper treatment even for the severe cases in hospitals. Therefore, the general public is advised to wear the mask, maintain social distancing, and use sanitizers. The COVID-19 mild infected patients may be isolated at home and can be taken care of by natural medicines. In this chapter, an attempt has been made to repurpose all potential natural drugs and natural Ayurvedic formulations that may be beneficial to combat viruses like the SARS-CoV-2, due to their antiviral and immune-modulator properties available under Indian traditional medicine and Chinese traditional medicine system for the effective treatment or prevention of COVID-19

 SARS-CoV-2 is an RNA virus responsible for causing pandemic COVID-19, which has taken on unprecedented proportions so far in global health and economic aspects. In this context, the search for effective drugs against SARS-CoV-2 has become a priority for the global scientific community, where the chymotrypsin-like picornavirus 3C-like protease (3CLpro, which is also named as main protease (Mpro), or only 3C) is a promising druggable target since it is crucial for the process of viral replication. Several 3CLpro inhibitors have been recently reported in the literature. Thus, peptidomimetics have emerged as a potential class for designing new effective drugs against COVID-19, in addition to lopinavir/ritonavir, in which these drugs are currently being investigated in clinical trials. In this chapter, we describe peptidomimetic and peptide-derived inhibitors of 3CLpro from SARS-CoV-2, and also SARS- and MERSCoV viruses, summarizing all relevant studies based on warhead groups utilization and SAR analysis for all of them in order to contribute to the development of compounds more selective, effective, and low-costs to combat these emerging viruses