As we await the development of a vaccine or biologic could we consider assessing the efficacy of the antimalarials or the other ‘FDA approved drugs’, as either treatments or prophylactics to prevent the Ebola virus from spreading further? While there can be no guarantee they will work (perhaps requiring adjusted dosage) they may be a last resort. It is possible there are other “non-antivirals” that are widely used in Africa that may also be effective against Ebola. Another example of where ‘non-antiviral’ FDA approved drugs have been found to have ‘anti-viral activity’ is for Hepatitis Virus B and D where the sodium taurocholate co-transporting polypeptide (NTCP) was identified as a receptor ¹⁶ and screening produced drugs such as azelastine, pioglitazone, glyburide, irbesartan and ezetimibe that inhibited the transporter and may provide potential treatments ^{17, 18} . Of these compounds, azelastine has been shown to possess in vitro activity against Hepatitis Virus B to date ¹⁸ .

The aforementioned screens of ‘FDA approved drugs’ ^{3, 8, 9} for Ebola virus activity, were far from comprehensive, covering only some of the known approved drugs currently in use. In an age where drug repurposing is in vogue ^{19– 23} and it can be facilitated by computational methods ^{24– 26} , it would seem a valuable resource for finding compounds active against the Ebola virus. For example, the recent pharmacophores developed for Ebola ¹⁰ and virtual screens ¹¹ could be used to computationally search larger datasets of FDA approved drugs and prioritize additional compounds for testing in vitro. Even using the known actives ( Figure 1) to perform simple similarity searches in a set of over 1300 Approved Drugs in a mobile app ( http://molmatinf.com/approveddrugs.html) could prioritize further compounds for testing ( Figure S1– Figure S7). For example molecules with structural similarity to chloroquine ( Figure S1) not only includes known actives like amodiaquine and hydroxychloroquine ³ but also suggests the antimalarials primaquine, halofantrine and the antihistamine chlorpheniramine. Molecules with similarity to amodiaquine include the kinase inhibitors neratinib and gefitinib while other kinase inhibitors have been suggested as having activity against Ebola virus ¹⁵ , these may not be readily accessible in Africa. Other compounds retrieved by similarity include the antimicrobial pentamidine ( Figure S3, Figure S4, Figure S7), the antiemetic trimethobenzamide ( Figure S3– Figure S7) and the antihistamine doxylamine ( Figure S5). Certainly more sophisticated and exhaustive searches than this could be tried. Deciding which molecules to use or test should also involve the physician’s perspective ²⁷ . Alternative treatments may also be found by studying those close to patients who may not have contracted the disease and are taking a drug for another chronic disease. Whether we can find a treatment for Ebola by serendipity is questionable but some of the published studies with known drugs might point us in the right direction of where to look. The opportunity to put already available drugs like those already identified ^{3, 8, 9, 11– 14} back on the table may be a useful tool for frontline doctors to have and is worthy of more urgent discussion and research.