ABSTRACT
The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy. Moreover, after more than 2 years, many populations are still under pressure of infection. Thus, a broader perspective in developing antiviral strategies is still of great importance. Inspired by the observed multiple benefits of heparin in the treatment of thrombosis, the potential of low molecular weight heparin (LMWH) for the treatment of COVID-19 have been explored. Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients, accordingly reducing lethality. Furthermore, several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection. These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates. In this review, we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection, focusing on the perspectives of developing heparin mimetics via chemical synthesis, chemoenzymatic synthesis, and bioengineered production by microbial cell factories. The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.
ABSTRACT
Previous researches suggested that polysaccharides from brown algae had anti-virus activity. We hypothesized that nature polysaccharide from marine plants might have the effect on anti-SARS-CoV-2 activity. By high throughput screening to target 3CLpro enzyme using polysaccharides library, we discover a crude polysaccharide 375 from seaweed Ecklonia kurome blocked 3CLpro enzymatic activity and shows good anti-SARS-CoV-2 infection activity in cell. Further, we show that homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro well and disturb spike protein binding to ACE2 receptor. The structure characterization uncovers that 37502 is alginate. These results imply that the bioactivities of 375 on SARS-CoV-2 may target multiple key molecules implicated in the virus infection and replication. The above results suggest that 375 may be a potential drug candidate against SARS-CoV-2.
Subject(s)
COVID-19 , Polysaccharides , Humans , Molecular Docking Simulation , Seaweed/chemistry , Virus Internalization/drug effectsABSTRACT
Due to the coronavirus disease 2019 (COVID-19) pandemic, the state of Texas-limited elective procedures to conserve beds and personal protective equipment (PPE); therefore, between March 22 and May 18, 2020, admission to the epilepsy monitoring unit (EMU) was limited only to urgent and emergent cases. We evaluated clinical characteristics and outcomes of these patients who were admitted to the EMU. Nineteen patients were admitted (one patient twice) with average age of 36.26 years (11 female) and average length of stay 3 days (range: 2-9 days). At least one event was captured on continuous EEG (cEEG) and video monitoring in all 20 admissions (atypical in one). One patient had both epileptic (ES) and psychogenic non-epileptic seizures (PNES) while 10 had PNES and 9 had ES. In 8 of 9 patients with ES, medications were changed, while in 5 patients with PNES, anti-epileptic drugs (AED) were stopped; the remaining 5 were not on medications. Of the 14 patients who had seen an epileptologist pre-admission, 13 (or 93%) had their diagnosis confirmed by EMU stay; a statistically significant finding. While typically an elective admission, in the setting of the COVID-19 pandemic, urgent and emergent EMU admissions were required for increased seizure or event frequency. In the vast majority of patients (13 of 19), admission lead to medication changes to either better control seizures or to change therapeutics as appropriate when PNES was identified.