Network analysis and molecular mapping for SARS-CoV-2 to reveal drug targets and repurposing of clinically developed drugs.

Novel coronavirus (SARS-CoV-2), turned out to be a global pandemic with unstoppable morbidity and mortality rate. However, till date there is no effective treatment found against SARS-CoV-2. We report on the major in-depth molecular and docking analysis by using antiretroviral (Lopinavir and ritonavir), antimalarial (Hydroxychloroquine), antibiotics (Azithromycin), and dietary supplements (Vitamin C and E) to provide new insight into drug repurposing molecular events involved in SARS-CoV-2. We constructed three drug-target-pathways-disease networks to predict the targets and drugs interactions as well as important pathways involved in SARS-CoV-2. The results suggested that by using the combination of Lopinavir, Ritonavir along with Hydroxychloroquine and Vitamin C may turned out to be the effective line of treatment for SARS-CoV-2 as it shows the involvement of PARP-1, MAPK-8, EGFR, PRKCB, PTGS-2, and BCL-2. Gene ontology biological process analysis further confirmed multiple viral infection-related processes (P < 0.001), including viral life cycle, modulation by virus, C-C chemokine receptor activity, and platelet activation. KEGG pathway analysis involves multiple pathways (P < 0.05), including FoxO, GnRH, ErbB, Neurotrophin, Toll-like receptor, IL-17, TNF, Insulin, HIF-1, JAK-STAT, Estrogen, NF-kappa, Chemokine, VEGF, and Thyroid hormone signaling pathway in SARS-CoV-2. Docking study was carried out to predict the molecular mechanism Thus, the potential drug combinations could reduce viral infectivity, viral replication, and abnormal host inflammatory responses and may be useful for multi-target drugs against SARS-CoV-2.

Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication.

This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia.

OBJECTIVE: Many patients with systemic lupus erythematosus (SLE) and fibromyalgia (FM) may spend less time exposed to the sun than healthy individuals and thus might have low vitamin D levels. It is known that hydroxychloroquine (HCQ) inhibits conversion of 25(OH)- to 1,25(OH)2-vitamin D both in vitro and in patients with sarcoidosis. We assessed winter serum 25(OH)- and 1,25(OH)2-vitamin D levels in patients with SLE and FM. METHODS: We recruited 25 consecutive female SLE and 25 female FM patients in London, Ontario, between January and March 2000. Subjects completed a brief questionnaire. Serum levels of 25(OH)-, 1,25(OH)2-vitamin D, and parathyroid hormone (PTH) were measured. RESULTS: In SLE patients mean 25(OH)-vitamin D was 46.5 nmol/l and mean 1,25(OH)2-vitamin D was 74.4 pmol/l. In FM patients these means were 51.5 nmol/l and 90.1 pmol/l, respectively. Serum 25(OH)-vitamin D levels did not significantly differ between SLE and FM patients, nor after adjusting for age and vitamin D, milk consumption, and sun block use. In 14 of the SLE patients and 12 of the FM patients 25(OH)-vitamin D levels < 50 nmol/l were found. SLE patients not using vitamin D supplements had lower 25(OH)-vitamin D levels than those who did. 1,25(OH)2-vitamin D tended to be lower in the SLE compared to the FM patients. This difference could be attributed to HCQ use: HCQ users (n = 17) had lower 1,25(OH)2-vitamin D levels than nonusers (n = 33); the mean adjusted difference was 24.4 pmol/l (95% CI 2.8-49.9). CONCLUSION: Half the SLE and FM patients had 25(OH)-vitamin D levels < 50 nmol/l, a level at which PTH stimulation occurs. Our data suggest that in SLE patients HCQ might inhibit conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D.