Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Patients With COVID-19

Inclusion Criteria: 1. Willing and able to provide informed consent for the trial, written, electronic, verbal or other method deemed acceptable by the institution and IRB. 2. 18 years of age or older. 3. If discharged from the hospital prior to Study Day 15 or if follow up is needed for study drug-related adverse event, willing to go to an outpatient facility if feasible or be in contact with the study team (phone call or other digital media) for remaining study assessments. 4. Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT-PCR) or other Food and Drug Administration (FDA)-cleared commercial or public health assay. 5. Hospitalized (in patient with expected duration ≥ 24 hours) 6. The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for 90 days after completion of brequinar administration. 7. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of brequinar. 8. ≤ 10 days since first COVID-19 symptom as determined by treating clinician. 9. Able to swallow capsules. 10. At least one COVID-19 symptom including but not limited to fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath, dyspnea, dysgeusia, or other symptom commonly associated with COVID-19. Exclusion Criteria: 1. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient. 2. Active malignancy other than squamous cell carcinoma; anticancer treatment such as chemotherapy or radiation therapy within the past month. 3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test. 4. Treatment with another DHODH inhibitor (e.g., leflunomide or teriflunomide), tacrolimus, sirolimus. 5. Platelets ≤150,000 cell/mm3. 6. Hemoglobin \< 10 gm/dL 7. Absolute neutrophil count \< 1500 cells/mm3 8. Renal dysfunction, i.e., creatinine clearance \< 30 mL/min 9. AST and/or ALT \> 1.5 ULN, or total bilirubin \> ULN 10. History of bleeding disorders or recent surgery in the six weeks preceding enrollment 11. Concomitant use of agents known to cause bone marrow suppression leading to thrombocytopenia 12. History of gastrointestinal ulcer, or history of gastrointestinal bleeding. 13. History of hepatitis B and/or C infection, active liver disease and/or cirrhosis. 14. Heart failure, current uncontrolled cardiovascular disease, including unstable angina, uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g. stroke, myocardial infarction, hospitalization due to heart failure, or revascularization procedure). 15. Life expectancy of \< 5 days in the judgment of the treating clinician. 16. Evidence of critical illness defined by at least one of the following: a. Respiratory failure requiring at least one of the following: i. Endotracheal intubation and mechanical ventilation, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies may not be able to be administered in setting of resource limitation) ii. Shock (defined by systolic blood pressure \< 90 mm Hg, or diastolic blood pressure \< 60 mm Hg or requiring vasopressors) b. Multi-organ dysfunction/failure.