The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing great threats to the world in many aspects. Effective therapeutic and preventive approaches including drugs and vaccines are still unavailable although they are in development. Comprehensive understandings on the life logic of SARS-CoV-2 and the interaction of the virus with hosts are fundamentally important in the fight against SARS-CoV-2. In this review, we briefly summarized the current advances in SARS-CoV-2 research, including the epidemic situation and epidemiological characteristics of the caused disease COVID-19. We further discussed the biology of SARS-CoV-2, including the origin, evolution, and receptor recognition mechanism of SARS-CoV-2. And particularly, we introduced the protein structures of SARS-CoV-2 and structure-based therapeutics development including antibodies, antiviral compounds, and vaccines, and indicated the limitations and perspectives of SARS-CoV-2 research. We wish the information provided by this review may be helpful to the global battle against SARS-CoV-2 infection.
Background
KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites.
Methods
We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg).
Results
Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts.
Conclusions
KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323.)
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