Abstract
Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year’s time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a “thrombotic storm,” much more than a “cytokine storm.” The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.
Highlights
Several viral proteins have been prioritised as SARSCoV-2 antiviral drug targets, such as the spike protein, the RNA-dependent RNA polymerase (RdRp), the main protease (Mpro), and the papain-like protease (PLpro).(5) the severe acute respiratory syndrome (SARS)-CoV-2 genome encodes four structural proteins, sixteen non-structural proteins (NSPs) that carry out crucial intracellular functions, and nine accessory proteins.[6]
Several viral proteins have been prioritised as SARSCoV-2 antiviral drug targets, such as the spike protein, the RNA-dependent RNA polymerase (RdRp), the main protease (Mpro), and the papain-like protease (PLpro).(5) the SARS-CoV-2 genome encodes four structural proteins, sixteen non-structural proteins (NSPs) that carry out crucial intracellular functions, and nine accessory proteins.[6]. In addition to the proteins mentioned previously above, the virus needs a foreign protein, the TMPRSS2 (Transmembrane Protease Serine 2), to infect the host’s cells
Mengist et al[10] described that inhibitors of the Mpro prevent the replication of SARS-CoV-2 in vitro. This effect is explained by the role of Mpro cleaving polyproteins translated from virus genomic RNA, yielding non-structural proteins that are necessary for assembling the viral replication transcription complex (RTC) for viral RNA synthesis in the host’s cells
Summary
Several viral proteins have been prioritised as SARSCoV-2 antiviral drug targets, such as the spike protein, the RNA-dependent RNA polymerase (RdRp), the main protease (Mpro), and the papain-like protease (PLpro).(5) the SARS-CoV-2 genome encodes four structural proteins, sixteen non-structural proteins (NSPs) that carry out crucial intracellular functions, and nine accessory proteins.[6] In addition to the proteins mentioned previously above, the virus needs a foreign protein, the TMPRSS2 (Transmembrane Protease Serine 2), to infect the host’s cells. The TMPRSS2 protein is considered an important therapeutic target, creating the potential for infection prevention if inhibited at the early stages of the infection. SARS-CoV and other coronaviruses use TMPRSS2 for their S protein activation, and the protease is expressed in SARS-CoV target cells throughout the human respiratory tract and other organs.[7,8,9].
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