Coronaviruses

Viral infections, which lack effective treatment, have posed an ongoing threat to human health. Most approved antiviral agents selectively target a single virus, providing a “one drug-one bug” solution. However, this approach has limited efficacy, particularly with emerging and re-emerging viruses with no specific, licensed antiviral drug or vaccine.

Since the outbreak of the COVID-19 pandemic, tremendous studies have focused on the effect of some (broad-spectrum) antiviral agents on this emerging virus. The concept of broad-spectrum antivirals refers to the group of drugs with the capability of combating more than one virus rather than “one drug-one bug” agents. This approach may offer a new horizon for the management of emerging viral threats.

Among BSAs, nucleotide and nucleoside analogs target enzymatic functions shared by some viruses, thus, inhibit their replication. An alternative approach of BSA agents is to target host factors commonly required by multiple viral pathogens, on which the viruses intimately rely. For example, anti-malarial agents (chloroquine and hydroxychloroquine) inhibit acidification of endosomes, an essential process for uncoating of some RNA viruses, kinase inhibitors impair intracellular viral trafficking, and statins attenuate replication of some enveloped viruses.

In this review, we will shed light on BSA agents with potential efficacy against SARSCoV- 2 infection. The time-consuming process of new drug development makes repositioning drugs, already approved for use in humans, the only solution to the epidemic of sudden infectious diseases as COVID-19.

COVID-19 was identified as a global pandemic by the World Health Organization on March 11, 2020. The uncontrolled transmission of COVID-19 (Coronavirus Disease-2019) in almost 215 countries has posed a serious health issue among the world population. Cases of COVID-19 have emerged from the Huanan seafood market in Wuhan, South China, in December 2019 and have been rapidly spreading throughout the world since then. In this chapter, we have tried to extract data from various research reports, WHO guidelines, and other published articles to summarize the prevention strategies for COVID-19. This disease causes varying degrees of illness in patients like fever, cough, sore throat, breathlessness, fatigue, and other related symptoms. There are no drugs or other therapeutics presently approved by the U.S. Food and Drug Administration (FDA) to prevent or treat COVID-19. Current clinical management includes infection prevention, control measures, and supportive care through anti-viral, anti-microbial as well as immuno-modulating drugs as first-line treatment, followed by symptomatic treatment and oxygen therapy. Besides drugs, plasma convalescent therapy is being utilized in serious patients, but most of the vaccine candidates developed against SARS-CoV-2 are in the clinical trial stages. It is necessary to identify the potential cases as early as possible and isolate the vulnerable population from the confirmed cases of COVID-19, to prevent the potential transmission of infection to healthy people, other patients, and health care staff. Early protection, early identification, early diagnosis, and early isolation are crucial to combat the COVID-19 outbreak. Improved personal protection and hygiene management at community levels should be officially endorsed to protect the population from infections. Proper arrangement of medical resources (i.e., oxygen supply, ventilators, PPE kits, gloves, sanitizer) can prevent the crucial damage caused by the disease. Another pressing need of the hour is to promptly discriminate patients with COVID-19 from other febrile diseases. Thus, the need of the hour is to develop rapid and accurate diagnostic technologies that can help the world to win the war against such viral pandemics.

Coronaviruses (CoVs) are associated with several infectious outbreaks in humans, beginning with severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012. Recently, the World Health Organization (WHO) announced the global outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in December 2019. There are currently no natural or synthetic drugs that inhibit SARS-CoV2. Because of the COVID-19 outbreak, many people have returned to the use of complementary or traditional medicinal therapies for prophylaxis or treatment. Herbal extracts and their purified natural compounds provide a platform for the development of novel antiviral candidates. Effective drugs may be designed based on the chemical structure of natural compounds that exhibit potential effects. Researchers have primarily focused on 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase, and spike (S) proteins as drug targets for SARS-CoV. Furthermore, phylogenetic studies of the viral genome have provided evidence of a close similarity between SARS-CoV2 and SARS-CoV1. Here, we review the literature with respect to plant extracts from different families that have been examined for antiviral activity against coronavirus diseases and explore the underlying mechanisms. We also discuss the structures of promising natural compounds representing different categories that serve as SARS-CoV chemical inhibitors. Hopefully, this chapter will provide a valuable tool for scientists interested in developing effective naturally derived anti-SARS-CoV-2 drugs for the management of COVID-19 development and progression.

Previous studies on the coronavirus (CoVID-19) have shown that respiratory symptoms such as fever, dry cough, and shortness of breath are mainly the common manifestations at the onset of the infection. These symptoms are largely similar to severe acute respiratory syndrome (SARS), which prevailed in 2003, and the Middle East respiratory syndrome (MERS) in 2012, indicating droplet and contact transmission to be the reason for transmission. However, it is widely accepted that a range of common attributes, like diarrhea, nausea, vomiting, and abdominal discomfort, can be observed among various affected populations, along with an early and mild onset commonly followed by typical respiratory symptoms. Increasing affirmation from several recent research works on SARS-CoV-2 has indicated that the gastrointestinal tract (intestine) epithelium is a favorable host to SARS-CoV-2 coronavirus particles. These findings are confirmed by the viral detection in biopsy specimens and stool samples of even the positive patients, thus explaining at least partially the gastrointestinal symptoms in the patients. Additionally, the wastewater-based epidemiology studies being done by various countries suggest that individuals can start shedding the virus particles in the feces long before any of the key symptoms could be manifested or before the patients could be clinically diagnosed. These findings have ignited the questions on potential recurrence and transmission of COVID-19 from persistent fecal shedding from the infected individuals.

Coronaviruses cause infections in birds and rodents, but these viruses have been able to infect the human in the last few decades. The Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 and the Middle East Respiratory Syndrome (MERS) in 2008 revealed the lethality of coronaviruses, as these viruses cross the species barrier and infect humans. An epidemic of novel Coronavirus that emerged in province Hubei, of which Wuhan was the epicenter, linked the number of cases with pneumonia-like symptoms to the seafood market in Wuhan, China. The human epithelial cells were used for the isolation of novel coronavirus that was diagnosed through the use of unbiased sequencing, later named nCoV-2019. Based on the information, there was evidence of transmission in humans that occurred because of close contact from the middle of December 2019. In recent times, the infection has been identified in other countries around the world, infecting millions of people. This review aims to assess the latest information regarding COVID-19 and compares it with previous knowledge reported regarding it. Most progress has been made on COVID-19, highlighting the specific structural requirements for its functions in the nCOV-19 life cycle and the mechanism behind its pathogenesis.

SARS-Corona-Virus-2 related disease (COVID-19) is a 2019 outbreak and was declared as a pandemic by WHO in March 2020. The high mortality rate in humans with SARS-CoV-2 has been attributed to its effects on major organs and primarily on the lungs. Therefore, it is extremely imperative to identify effective strategies for the prevention and treatment that can cease or reverse the inflammatory process associated with acute lung injury, ARDS, and multi-organ failure in COVID-19 patients. Inflammation to lungs through cytokine storm [also known as cytokine release syndrome (CRS)] is mediated through many cytokines, and IL-17 is one amongst them. We have experimentally demonstrated IL-17 responses in autoimmune/inflammatory disorders through Boerhavia erecta L in vitro and in vivo models recently, and further, propose this herbal medicine in this review chapter as a potential treatment option for mild to moderate acute respiratory distress syndrome (ARDS) in COVID-19 patients.

Coronaviruses affect both humans and animals, causing respiratory, enteric, hepatic, and neurological diseases. Until the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, coronaviruses were known to cause very mild infections in humans. However, the ongoing novel coronavirus disease (COVID- 19) that emerged in December 2019 from Wuhan, Hubei province, China, is several folds critical than the disease caused by its predecessors, SARS and MERS coronaviruses of 2002 and 2012, respectively. The evidence shows that all the human coronaviruses of this century, including the ongoing pandemic SARS-CoV-2, were the result of zoonosis, crossing the animal species barrier, causing high morbidity and mortality in the human population. A large number of studies have provided an understanding of earlier SARS-CoV and MERS-CoV induced pathogenesis and host immune response. Immunopathogenesis of current SARS-CoV-2 has also been reported to a significant extent since its emergence. It is evident from the studies reported to date that all the above three human coronaviruses share similarities with respect to clinical symptoms caused, pathological conditions induced, and host immune response that leads to the disease progression to a larger extent. However, certain pathological features associated with SARS-CoV-2 infection are distinct and fatal from the features caused by the other two human coronaviruses. This chapter focuses on the studies related to immune response, molecular pathogenesis of all three human coronaviruses with an emphasis on SARS-CoV-2 and the immune evasion strategies stimulated by individual viral proteins and their driven mechanisms.

Temporomandibular disorders (TMDs) are a group of disorders related to pain and dysfunction that affect the temporomandibular joint (TMJ) and the masticatory system. TMD patients often suffer from orofacial pain and have symptoms that are less specific, including ear pain and ear fullness, tinnitus, dizziness, neck pain, and headache. Thus, individuals with TMD and orofacial pain deserve special attention, since neurological events such as headache, tinnitus, and muscle pain, which are present in these conditions, can also be found in cases of COVID-19. In addition, mental health disorders, such as anxiety and depression, are more common in patients with TMD than in the general population. Consequently, individuals with psychological disabilities, such as TMD patients, may have their pain perpetuated as a result. COVID-19 is not only affecting physical health — it has brought direct and indirect psychological and social consequences that can influence mental health both during the pandemic and in the future. Therefore, it is believed that psychological factors in connection with the pandemic may lead to a great risk of developing, worsening, and prolonging TMD, since these factors can lead to autonomic responses that result in sleep disorders. This chapter will address the impact of the COVID-19 pandemic on the mental health of TMD patients, focusing on brain changes involving the trigeminal pathway and maladaptive changes in the default mode network (DMN).