# Prioritization of Drugs for Fungal Keratitis Eye Infections: An In-Silico Analysis
## 1 Introduction  
Cornea inflammations caused by fungal infections (fungal keratitis or keratomyosis) remain one of the most ethereal and challenging infections for ophthalmologists to diagnose and treat [1]. These fungal keratitis (FK) infections are more likely to perforate the cornea and more virulent than other bacterial keratitis infections [2]. Many cases of ocular trauma are reported as major predisposing factors of fungal keratitis infections in developing countries, including India and Ghana [3]. The incidence of fungal keratitis has been reported to range between 25.6% and 36.7% in various parts of India [4; 5; 6]. FK infections are believed to usually occur in the population engaged in agricultural or outdoor work where the fungal conidia of plant or animal origin, including dust particles, might directly lodge in the corneal stroma and allow exogenous fungi invasions [7]. It is evident that species of filamentous fungi, such as _Aspergillus_ and _Fusarium_, are most commonly associated with keratitis in tropical countries, including India [8; 9]. _Aspergillus_ is a very large genus,including more than 185 species, to which humans are frequently exposed. Certain _Aspergillus_ species, mainly _A. flavus, A. fumigatus, A. terreus_ and _A. niger_, have long been regarded as important pathogens in eye infections, especially keratitis [10]. _Aspergillus_ strains are among the most frequent organisms that cause fungal keratitis among rural agricultural workers. Recent molecular studies revealed that the spectrum of _Aspergillus_ species capable of causing mycotic keratitis is much wider than earlier believed, including _A. tamarii_[11], _A. nomius_[12], _A. tubingensis_[13] and _A. brasiliensis_[14]. The major groups of antifungal drugs are azoles and polyenes, which are fungistatic with interference in protein synthesis and fungicidal with an effect on cell wall function, which has been accepted for the treatment of keratitis [15; 16]; however, their efficacies are limited for several reasons, including the increasing resistance to antifungal drugs, their limited effect on certain fungal species, and their exclusively topical route of administration, which limits the use of those drugs to treat the superficial fungal infections, as opposed to deep fungal invasions [17]. The presence of deep fungal lesions and invasions may necessitate a systemic route of administration, such as intravenous or oral administration. Further, the emergence of resistance and a high blindness rate in keratitis warrants a careful consideration and selection of anti-fungal agents, the identification of novel therapeutic drug targets, or the design of novel anti-fungal agents for better therapy. The inhibition of fungal RNA synthesis might also exert antifungal effects through a reduction in subsequent protein synthesis. Indeed, the agent flucytosine exerts its antifungal effects at least partly through inhibition of RNA synthesis, suggesting that this target might be exploited for anti-fungal therapy [18]. A few in-vitro studies [19; 20; 21; 22] have reported that a combination of amphotericin B and rifampicin, an antibacterial agent that inhibits RNA polymerase, synergistically interacts against a variety of fungi. In line with this result, the DNA dependent RNA polymerase (RNAP) that is responsible for transcribing DNA has been considered as a direct or indirect target for the treatment of various fungal infections, including fungal keratitis [23]. In last few decades, structure based virtual screening has become prominent in drug discovery, particularly in molecular docking studies [24]. Thus, in the present study, polyenes and azoles were selected for their molecular docking and better binding affinities against RNAP from _hyaloluphylomycesetes_ causing keratisis. Namely, _A. flavus_ and _A. fumigatus_, are explored.