**6. Challenges in drug discovery for infectious diseases**

The major challenge in drug discovery for infectious diseases is the mutation in superbugs which make them evolve rapidly. Despite the availability of structural information of 62,206 bacterially derived proteins in PDB, mutational changes in these structures necessitate continuous research in 'omics studies. Moreover, the virus-derived proteins are only 9603 in number [20] leading to a reduced success rate of structure-based design of antiviral drugs. Nevertheless, many QSAR projects fail at the model building stage due to a lack of interdisciplinary application during the execution of the project. Similarly, a considerable challenge at the stage of *in vitro/in vivo* screening is the penetration of molecules into the bacterial cell, especially in Gram-negative species. However, these challenges may be countered with a diversified chemical space which is again a challenge for combinatorial chemistrybased chemical libraries. Therefore, biodiversity needs to be explored for identifying novel pharmacophores and associated anti-infective drugs.

#### **7. Future perspectives**

Highly diversified chemical space is a must for identifying novel pharmacophores which can be obtained through engineering biodiversity. Phytochemical hybridization [33] and phytochemical engineering [34] offer a great advantage to generate diverse semisynthetic chemical libraries which may be fruitful in identifying novel anti-infective pharmacophores. Further, nanotechnology is an emerging technology through which nanoprobes may be utilized to analyze microbes. Hence, HTS incorporated with nanotechnology may improve the efficiency of HTS [16]. Similarly, microfluidic technology may enable the use of a single platform to combine genome sequencing, mining, and uHTS. Thus, this technology may open up unique opportunities for anti-infective drug discovery at the level of single cell [35]. Further, given the urgency of the coronavirus (CoV) outbreak, HTS methodology using two types of mild CoV, HCoV-OC43 and MHV, was developed as a valuable tool for the rapid identification of promising drugs against CoV without the drawbacks of level three biological confinements. The luciferase reporter gene is introduced into HCoV-OC43 and MHV to indicate viral activity, and hence the antiviral efficiency of screened drugs can be quantified by luciferase activity. Compounds with antiviral activity against both HCoV-OC43 and MHV are further

*High-Throughput Screening for Drug Discovery toward Infectious Diseases: Options and Challenges DOI: http://dx.doi.org/10.5772/intechopen.102936*

evaluated in SARS-CoV-2 after structural optimizations. This system allows largescale compounds to be screened to search for broad spectrum drugs against CoV in a high-throughput manner, providing potential alternatives for clinical management of SARS-CoV-2 [36].
