Prior to the first severe acute respiratory syndrome (SARS), a limited number of coronaviruses were known to spread in humans, since they causu only mild illnesses, such as the common cold. After the SARS pandemic in 2003, coronaviruses apparently cross species barriers and cause infections that threaten human life.
The 21st century has experienced the spread of two previously unrecognized coronaviruses worldwide with high pathogenicity, namely severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome corona Virus (MERS-CoV), as well as the 2019-nCoV, which is still spreading in the world, especially in China.
Since November 2002 in China, SARS coronavirus has experienced unprecedented transmission from person to person, accompanied by high mortality. Joint efforts worldwide have enabled rapid identification of SARS coronaviruses, and have made significant scientific advances in epidemic prevention in a short period of time. In addition, zoonotic transmission of SARS from December 2003 to January 2004 provided researchers with a line of insight into the origin of this new coronavirus. It is worth noting that the SARS pandemic was announced in 2004 when no more infections were detected. Subsequently, some suspected SARS-Cov viruses found in bats showed the ability to infect human cells without pre-adaptation, suggesting that SARS-Cov or similar SARS-Cov viruses may reappear. Ten years later, in June 2012, in Saudi Arabia, another highly pathogenic novel coronavirus, MERS-CoV, was isolated from the sputum of a male patient who died of acute pneumonia and renal failure. Nosocomial infections have been reported, and international travel has caused the MERS-CoV virus to spread to countries outside the Arabian Peninsula, making it a global pathogen. In May 2015, the Middle East respiratory syndrome broke out in South Korea due to a person returning from the Middle East. Based on lessons learned in the management of the SARS epidemic over the past decade, unprecedented advances have been made in revealing the biological properties of MERS. Scientific advances have enabled us to make rapid and systematic progress in understanding the epidemiology and pathogenesis of MERS-CoV disease.
The common characteristics of SARS-CoV and MERS-CoV
SARS-CoV and MERS-CoV share several important common characteristics— preferential viral replication of the lower respiratory tract and viral immunopathology, which contribute to hospital-wide transmission.
This article mainly focuses on the epidemiology and pathogenesis of these viruses, including our current understanding of their biological characteristics, transmission, and replication in the host. Covs' S protein plays a key role in viral infection and pathogenicity. As the key surface trimeric glycoproteins of Covs, they are guided into host cells. This article reviews the structure and function of S protein and the therapeutic methods targeting S protein. In addition, we will explore how the interaction between coronavirus and host leads to pathogenic outcomes, discuss potential treatment options, and describe the development of prevention and treatment strategies that are closely related to the pathogenic process for SARS-CoV and MERS-CoV. Although several potential therapies for SARS and MERS have been identified in animal and in vitro models, the lack of human clinical trials has hindered the development of these potential countermeasures.
An overview of 2019-nCoV
In the context of the current transmission of new coronaviruses, in order to control the spread of the virus and improve the prognosis of patients, it is urgent to develop public health and medical control methods. Whole-genome sequencing revealed that the new coronavirus (2019-nCoV) has very strong sequence similarity with its close relative, SARS coronavirus (SARS-CoV). The spike protein of 2019-nCoV infected host target cells showed some key non-synonymous mutations relative to SARS-CoV, which may lead to the less effectiveness of existing treatment methods and drugs targeting SARS coronavirus spike protein for 2019-nCoV. In addition, key drug targets, including the RdRp protein and 3CLpro protein, share a very high sequence similarity of greater than 95% with SARS-CoV. Therefore, this article proposes four potential drugs (ACE2 polypeptide, Remdesivir, 3CLpro-1 and a new vinyl sulfone protease inhibitor) that may be used to treat 2019-nCoV infection. At the same time, this article also summarizes the previous work on the drug research of these targets, hoping to provide guidance for future research on broad-spectrum anti-new coronavirus drugs.
To be continued in Part II…