Primary studies included in this systematic review

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PEP CoV-2/HCQ4COV19 (Study 2) (Barcelona Postexposure Prophylaxis Study against SARS-CoV-2 - Study 2)

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Unclassified

Authors Lee PI , Hsueh PR
Journal Journal of microbiology, immunology, and infection
Year 2020
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ABSTRACT: Coronaviruses are enveloped RNA viruses that are widely detected in mammals and birds, and commonly denoted in etiologies of upper respiratory tract infections in humans.Two potentially dangerous zoonotic coronaviruses have emerged in the past two decades. The severe acute respiratory syndrome coronavirus (SARS-CoV), originating from China, was responsible for the first outbreak that extended from 2002 to 2003. The second outbreak occurred in 2012 in the Middle East and was caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). A new strain of coronavirus, designated as the 2019 novel coronavirus (2019-nCoV), emerged during the third outbreak in Wuhan, China, at the end of 2019. Symptoms of pneumonia with unknown etiology were reported in several patients. The infection was epidemiologically linked to the Huanan seafood market in Wuhan.6 Similar to the SARS-CoV and the MERS-CoV, bats have been denoted as the likely primary reservoirs of the 2019-nCoV based on its similarity to bat coronaviruses.7 The intermediary reservoir is yet to be denoted. The pertinent and critical factor for an emerging virus is its pandemic potential. Efficient human-to-human transmission is a requirement for large-scale spread of a new virus. The proportion of patients with mild symptoms of illness is another important factor that determines our ability to identify infected individuals and to prevent the spread of virus. Identification of transmission chains and subsequent contact tracing are further complicated when several infected individuals remain asymptomatic or mildly symptomatic. A key factor for efficient human-to-human transmission is the ability of the virus to attach to human cells. Coronaviruses use a spike protein for attachment to host cells.8 Apparently, the 2019-nCoV uses the same human angiotensin-converting enzyme 2 receptor as the SARS-CoV,5 whereas the MERS-CoV used dipeptidyl peptidase (also known as CD26). An efficient human-to-human transmission involves multiples routes of transmission, including droplet transfer, direct contact, and indirect contact. A limited human-to-human transmission may require a high infective dose and a significantly close contact with an infected person as prerequisites

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LOTUS China (Lopinavir Trial for Suppression of SARS-Cov-2 in China)

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Publication Thread

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Primary study

Unclassified

Authors Xia S , Liu M , Wang C , Xu W , Lan Q , Feng S , Qi F , Bao L , Du L , Liu S , Qin C , Sun F , Shi Z , Zhu Y , Jiang S , Lu L
Journal Cell research
Year 2020
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The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.

Publication Thread

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Primary study

Unclassified

Authors Beigel JH , Tomashek KM , Dodd LE
Journal The New England journal of medicine
Year 2020