ABSTRACT
While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo . We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters.
ABSTRACT
Among the deadliest pandemics in history, coronavirus disease 2019 (COVID-19) has wreaked havoc on human lives, economies and public health systems worldwide. To temper its effects, diagnostic methods that are simple, rapid, inexpensive, accurate, selective and sensitive continue to be necessary. In our study, we developed an electrochemical biosensing platform based on gold clusters, mercaptoethanol, the spike protein of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antigen and bovine serum albumin-modified glassy carbon electrode able to detect the SARS-CoV-2 spike antibody. Moreover, during the detection of the SARS-CoV-2 spike antibody in spiked-real samples, the anodic signal of the produced biosensor at 0.85 V decreased as the amount of the SARS-CoV-2 spike antibody increased. Meanwhile, the recovery and relative standard deviation values for saliva and oropharyngeal swab samples were 97.73% and 3.35% and 102.43% and 4.63%, respectively. In 35 min, the biosensing platform could detect 0.03 fg/mL of the SARS-CoV-2 spike antibody in synthetic media and spiked-saliva or -oropharyngeal swab samples. The method thus issues a linear response to the SARS-CoV-2 spike antibody from 0.1 fg/mL to 10 pg/mL. The cross-reactivity studies with spike antigens of Middle East respiratory syndrome-coronavirus and influenza A and the antigen of pneumonia confirmed the excellent selectivity of the proposed method. The developed method was compared with the lateral flow immunoassay method in terms of sensitivity and it was found to be approximately 109 times more sensitive. Biosensing mechanism of the platform to the SARS-CoV-2 spike antibody.
Subject(s)
Antibodies, Viral/analysis , COVID-19 Serological Testing/instrumentation , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/analysis , Antibodies, Viral/immunology , Biosensing Techniques/instrumentation , COVID-19/immunology , Electrochemical Techniques/instrumentation , Equipment Design , Humans , Hydrogen Bonding , Models, Molecular , SARS-CoV-2/immunology , Saliva/virology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
Amid the global threat caused by the coronavirus disease 2019 (COVID-19) pandemic, developing sufficiently rapid, accurate, sensitive and selective methods of diagnosing both symptomatic and asymptomatic cases is essential to alleviating and controlling the pandemic's effects. This article describes an electrochemical immunoassay platform developed to determine the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike antibody by using gold-clusters capped with cysteamine, glutaraldehyde, the spike protein of the SARS-CoV-2 antigen and bovine serum albumin on a glassy carbon electrode. The electrochemical oxidation signal of the antigen-based immunosensor at 0.9 V was used to detect the SARS-CoV-2 spike antibody. When saliva and oropharyngeal swab samples were analysed, the recovery and relative standard deviation values were 96.97%-101.99% and 4.99%-5.74%, respectively. The method's limit of detection relative to the SARS-CoV-2 spike antibody in synthetic media and in saliva or oropharyngeal swab samples was 0.01 ag/mL, while the immunosensor's linear response to the SARS-CoV-2 spike antibody varied from 0.1 to 1000 ag/mL. The cross-reactivity of the Middle East respiratory syndrome-coronavirus spike antigen was evaluated after being immobilised onto the functionalised gold-cluster based sensor, indicated that the good specifity of the produced immunosensor.