ABSTRACT
In December 2019, a small number of cases of pneumonia of unknown origin were recognized in the city of Wuhan, China. Soon, the disease, whose etiological factor was recognized as a coronavirus SARS-CoV-2, had spread across the world. The resulting CoV-associated diseases were classified by the WHO as COVID-19, and a pandemic was declared in March 2020. By 25 November 2021, there have been nearly 256.8 million of confirmed cases of COVID-19 around the world, including 5.17 million deaths. This review focuses on basal characteristics of the SARS-CoV-2 virus - its structure, replication cycle, variants and course of infection. It also briefly characterizes the currently recommended drugs and vaccines. Coronaviruses (CoVs) are a group of RNA viruses with a characteristic solar corona image observable on electron micrographs. SARS-CoV-2 possesses high affinity to human angiotensin converting enzyme 2 (ACE2) which serves as a cellular entry receptor. Its replication in human cells is accompanied by a high mutation rate. Six variants of SARS-CoV-2 have been found to be associated with essential changes of global public health significance; they are referred to as 'variants of concern' (VOC). The main route of transmission is through respiratory droplets. Although COVID-19 presents primarily as a respiratory disease, it can affect various other organs and systems that present the ACE2 protein to which the virus binds, including the heart, kidneys, intestines, liver, muscular and nervous system. COVID-19 infection can result in uncontrolled systemic hyperinflammation caused by release of a large amount of pro-inflammatory cytokines (a 'cytokine storm'), which can lead to multi-organ failure, rapid clinical deterioration and even death. Around 30% of those infected with SARS-CoV-2 remain asymptomatic, with the majority of patients demonstrating only mild or moderate symptoms; however, about 20% develop severe or critical disease. Three main groups of medications are currently recommended for therapy of COVID-19: monoclonal antibodies against the S protein of SARS-CoV-2, antiviral drugs and immunosuppressants which inhibit the cytokine storm. At present, the safest and most cost-effective way to prevent COVID-19 illness is a preventative vaccination.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Peptidyl-Dipeptidase A , Respiratory Aerosols and DropletsABSTRACT
The COVID-19 pandemic, caused by SARS-CoV-2 - a novel and highly infectious coronavirus, has been spreading around the world for over a year, and poses a serious threat to the public health. Numerous studies have revealed the genome, structure and replication cycle of the SARS-CoV-2 virus as well as the immune response to infection. Data from these studies provide a firm basis for the development of strategies to prevent the further spread of COVID-19, as well as to synthesize effective and safe vaccines and drugs. First and foremost, vaccines are needed to control the COVID-19 pandemic. According to data released by WHO, at the beginning of 2021 there were 63 potential vaccines under clinical examinations, and over 172 in preclinical trials. The most promising vaccines are mRNA-based: Comirnaty (Pfizer- BioNTech), COVID-19 Vaccine (Moderna/NIAID) and CVnCoV (CureVac);vector vaccines: COVID-19 Vaccine (AstraZeneca/Oxford University), Gam-COVIDVac (Gamaleja Institute, Russia) and JNJ-78436735/Ad.26.COV2.S. (Johnson & Johnson), and NVX-CoV2373 recombinant subunit vaccine (Novavax). The following groups of drugs potentially may be used in the COVID-19 therapy: Antiviral drugs with different mechanisms of action - blocking the binding of SARS-CoV-2 to its specific receptor on cell membrane (angiotensin coverting enzyme 2;ACE2) and inhibiting viral entry into host cells (umifenovir, chloroquine, hydroxychloroquine, camostat mesylate and nafamostat);drugs that inhibit viral replication (inhibitors of RNA-dependent RNA polymerase, e.g. remdesivir, favipiravir, ribovirin and molnupiravir;protease inhibitors, e.g. Kaletra);immunomodulating drugs (humanized monoclonal anticytokine antibodies, e.g. adalimumab, infliximab, tocilizumab and anakinra;JAK kinase inhibitors - ruxolitinib and baricitinib), anti-inflammatory drugs (glucocorticosteroids), and neutralizing monoclonal antibodies targeting the SARS-CoV-2 spike protein (S). Moreover, low molecular weight heparin is used for prophylactic and therapeutic purposes. © 2021 Polish Pharmaceutical Society. All rights reserved.
ABSTRACT
In December 2019, a novel highly pathogenic coronavirus SARS-CoV-2, which can be transmitted from person to person, was discovered in patients with infectious respiratory disease in Wuhan, Hubei Province, China. The disease, now known as the 2019 coronavirus disease (COVID-19), has spread rapidly around the world causing a pandemic. This survey presents basic information on the structure and replication cycle of SARS-CoV-2. Fundamental discoveries in genetics and molecular biology of the virus paved the way to design and development of molecules that would act as potential therapeutic agents for COVID-19. The virus belongs to the β-coronavirus 2B lineage. Comparison of the SARS-CoV-2 genome sequence and other available β-coronavirus genomes suggests that it may have evolved naturally from the RaTG13 bat strain of coronaviruses. The virus has a positivesense single-stranded RNA that acts as mRNA following cellular entry and is completely dependent on the translation machinery of the host cell. The genomic RNA of SARS-CoV-2 comprises 14 open reading frames (ORFs). Two main ORFs, ORF1a and ORF1b, encompass two-thirds of the genome and are translated to polyproteins pp1a and pp1ab, respectively. These polyproteins are processed by viral proteases (papain-like protease and chymotrypsin-like protease), to produce 16 nonstructural proteins (Nsp). The remaining one-third of the genome encodes four major structural proteins: Spike (S), membrane (M), envelope (E) and nucleocapsid (N), and seven accessory proteins. SARS-CoV-2 infects human cells by binding to its receptor, i.e. angiotensin converting enzyme 2 (ACE2) at the cell surface through the receptor binding domain of its S protein. Following the entry into the host cell, the genetic material is released into the cytoplasm, and the synthesis of viral proteins necessary for the further process of replication and translation takes place. After mature virus particles are formed, they travel in Golgi vesicles to the host cell membrane where they are released into extracellular space by exocytosis. With the continued spread of SARS-CoV-2 around the world, thousands of mutations have been identified, some of which have relatively high incidences. The following proteins exhibited the highest mutation density: N, S, Nsp2, Nsp3, Nsp5, Nsp6, Nsp7, Nsp12, Nsp13, Orf3 and Orf8. The changes in SARS-CoV-2 proteins caused by mutations can not only affect virus transmission, pathogenesis, and immunogenicity, but also give rise to false negative diagnoses and drug resistance. © 2021 Polish Pharmaceutical Society. All rights reserved.
ABSTRACT
Coronaviruses have been known to the mankind for decades. In the past, they were thought to cause mild infections of the upper respiratory tract. The emergence at the beginning of the 21st century of two highly transmissible and pathogenic β-coronaviruses, i.e. Severe Acute Respiratory Syndrome Coronavirus (SARS- CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), causing respiratory failure leading to the death of a large number of patients, highlighted a significant threat to the entire world. The 21st century has brought events at a catastrophic scale - the COVID-19 pandemic. SARS-CoV-2 virus from the Coronaviridae family responsible for the disease, appeared at the end of 2019 in Wuhan, China, and in a short time has lead to the devastation of lives of millions of people around the world. A comparison of the SARS-CoV-2 genome sequence and other available β-coronavirus genomes indicates the closest association of SARS-CoV-2 with the BatCov RaTG13 bat coronavirus strain (96% similarity). Therefore, it is suggested that SARS-CoV-2 virus may have evolved naturally from the RaTG13 virus strain transmitted by bats. The consequences of the COVID-19 pandemic include, among others, a significant number of illnesses and fatalities, inefficiency of health care systems, mental disorders and unprecedented methods of fighting the pandemic requiring closure of large sectors of the economy and a drastic reduction of interpersonal contacts. This survey presents basic information about β-coronaviruses. It also describes the course of COVID-19, taking into account a wide range of clinical symptoms from the respiratory, cardiovascular, digestive, reproductive and nervous systems, kidneys and skin. In addition, problems of mental disorders related to the current situation, both in patients and medical personnel as well as in general population, are discussed. The most common symptoms of COVID- 19 in children are presented. The article also describes methods used for a diagnosis of the SARS-CoV-2 infection, and disturbances in hematological, biochemical, hemostatic and inflammatory parameters found in COVID-19 patients, emphasizing their role as prognostic factors for the severity of the disease. © 2021 Polish Pharmaceutical Society. All rights reserved.
ABSTRACT
The renin-angiotensin-aldosterone system (RAS) plays a significant role in the regulation of the water and electrolyte balance. Renin from the kidneys converts angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II. The activation of AT1 receptors by angiotensin II causes vasoconstriction, an increase in aldosterone secretion, and an increase in the reabsorption of sodium ions in nephrons, leading to elevation of the blood pressure. Angiotensin II promotes oxidative stress, growth and proliferation of cells, stimulates coagulation, inhibits fibrinolysis, and intensifies inflammatory processes. The ACE-angiotensin II-AT1R pathway is balanced by angiotensin converting enzyme 2 (ACE2), which degrades angiotensin I to angiotensin (1-9) and angiotensin II to angiotensin (1-7). Angiotensin (1-7) and angiotensin (1-9) pathways exert protective effects by activating, respectively Mas and AT2 receptors. ACE and ACE2 also have intimate roles with the plasma kallikrein-kinin system (KKS), a hormonal pathway that modulates the intrinsic blood coagulation system, endothelial cell growth and angiogenesis, the complement pathway and RAS. The appearance in Wuhan, China, of the first cases of SARS-CoV-2 infections at the end of 2019 launched a series of intensive studies, which proved that the virus invades host cells using ACE2 as a specific receptor. This survey presents basic information on the structure and tissue distribution of ACE2 and the role this enzyme plays in pathogenesis of COVID-19. A particular emphasis is given to pathophysiological effects of the functional superiority of the ACE → angiotensin II → AT1 receptor axis over the pathway ACE2 → angiotensin II → angiotensin (1-7) → Mas receptor. Such disharmony is a consequence of SARS-CoV-2 induced ACE2-downregulation. In the era of the expanding COVID-19 pandemic, intensive research is conducted not only on vaccines and antiviral drugs, but also on compounds that can restore the functional balance between angiotensin II and angiotensin (1-7). © 2021 Polish Pharmaceutical Society. All rights reserved.
ABSTRACT
In December 2019, an outbreak of pneumonia cases was reported in Wuhan, China. The new virus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) - a highly pathogenic strain of coronaviruses - was isolated on 7 January 2020 and identified as the cause of the outbreak. The SARS-CoV-2 virus rapidly spread across China and many other countries and lead to an unprecedented public health crisis worldwide. While 80% of infected individuals remain asymptomatic or develop only mild symptoms, the remaining 20% experience a rapid progression of the disease and severe/critical clinical condition that could lead to death. In patients with severe/critical phase of COVID-19, the SARS-CoV-2 virus has been shown to disrupt the normal immune response, leading to dysregulation of the immune system function and development of uncontrolled hyperinflammatory processes. Several studies highlight relevant changes occurring both in innate and adaptive immune system. Recent data indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to the disease severity and mortality. It was demonstrated that patients with severe/critical phase of COVID-19 exhibit lymphopenia, a decrease in number of NK cells, eosinophils and basophils, an increase in inflammatory monocytes and neutrophils, an impaired interferon-α production and activity, no detectable circulating interferon-β, and massive production of proinflammatory cytokines, commonly known as cytokine storm. Many reports suggest that acute respiratory depression syndrome, cardiac dysfunction, hepatic impairment, acute kidney injury, coagulopathies, and multi-organ failure, that are characteristic of severe/critical COVID-19, are not due to direct effects of SARS-CoV-2, but result from the exaggerated cytokine release in response to viral infection. A better understanding of the pathophysiology and immune system dysregulation associated with cytokine storm and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and to develop effective vaccines and drugs. In addition, the knowledge on the processes induced by SARS-CoV-2 infection opens a door for the development and introduction of predictive diagnostic tests that enable the prognosis of the course and severity of the disease. © 2021 Polish Pharmaceutical Society. All rights reserved.