Preprints-COVID-19: Interesting COVID-19 Preprint Studies That Have Yet To Be Peer-Reviewed (Volume 1)
: Currently on a daily average there are about almost 140 research studies being published on numerous preprint servers but many do not even get the attention of science or medical journals unless they can afford the high fees charged by some of these journals or they have the backing of huge pharmaceutical companies behind them or have access to the right contacts as there is a lot of greed, nepotism and cronyism at play in the research publishing arena. Thailand Medical News starts this new series of fast and summarized reviews of various preprint studies published and hope that it will benefit both researchers and readers.
1.The Human Coronavirus 229E Spike Proteins Undergoes Antigenic Evolution To Evade Human Host Immune Response.
Despite intense interest about antibody immunity to coronaviruses, there is little data to show if coronaviruses truly evolve to escape such immunity, and if so, how rapidly.
The study team in this research attempts to address this by characterizing the historical evolution of human coronavirus 229E. They identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. The study team tests these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these "future" viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8-17 years later. The decreased neutralization of "future" viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.
: A human coronavirus evolves antigenically to escape antibody immunity
2. Cellular Oxidant N-Chlorotaurine Could Be Used As A Prophylatic And Therapeutic Inhalant Against SARS-CoV-2.
Austrian researchers from the Medical University of Innsbruck have found that N-chlorotaurine (NCT), a long-lived oxidant generated in activated cells of the innate immune system, namely neutrophilic and eosinophilic granulocytes and monocytes could be used as a potential prophylaxis and treatment agent against the COVID-19 disease.
N-chlorotaurine acts as an antiseptic agent that can be synthesized chemically and applied topically on different infected body sites. Even treatment of the lower respiratory tract via inhalation, which has been in development in the last years, was well tolerated in a recent phase I clinical trial.
The study team demonstrated the activity of NCT against viruses causing acute respiratory tract infections, in fact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus.
N-chlorotaurine revealed broad virucidal activity against all viruses tested. In the presence of o
rganic proteinaceous material simulating body fluids, this activity was enhanced by transchlorination mechanisms so that significant inactivation of viruses could be achieved within 1 to10 minutes.Inhalation of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.
: N-chlorotaurine, a novel inhaled virucidal antiseptic is highly active against respiratory viruses including SARS-CoV-2 (COVID-19)
3. Biomarker Cardiac Troponin T Can Be Used To Determine COVID-19 Severity And Mortality In Hospitalized Patients.
Chinese researchers from Fudan University conducted a study to analyze the potential risk factors related to the severity of the disease and 28-day mortality of patients.
A total of 122 COVID-19 patients hospitalized in Wuhan Third Hospital from 26 January 2020 to 16 March 2020 were included in this retrospective study. Clinical data of patients were retrospectively analyzed, and the risk factors associated with disease severity and 28-day mortality were screened by cox regression analysis. Of all 122 patients, the median age was 64 years old (interquartile range, 57- 71 years old).
The study found that compared with non-severe patients, severe patients had higher indices like cardiac troponin T and respiratory rate. In cox regression analysis, cardiac troponin T correlated with 28-day mortality most.
The study team concluded that
abnormal cardiac troponin T value after admission were in strong correlation with 28-day survival status.
: Cardiac Troponin T as the Underlying Risk Factor Associated With Disease Severity and Mortality in Patients With Coronavirus Disease 2019
4. Human Surfactant Protein D Could Be A potential Antiviral To treat COVID-19.
The Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with SARS-CoV infection. . Studies have suggested the ability of human SP-D to recognize spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells.
Past studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo models.
This study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 microg/ml).
The study findings results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.
BioRxiv: Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro
Another preprint study also was published supporting the usage of Human Surfactant Protein D as potential inhibitors of SARS-CoV-2
That study also aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2.
The study team used both computational docking studies and in vitro studies. rfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR.
In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5 micro M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 micro M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5 micro M rfhSP-D.
These results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.
: A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples
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