Table 2.

Drug targets (genes/proteins), their products and functional activities and mode of action of anti-TB drugs.

Drug targets	Size (bp)	Protein length	Molecular mass (Da)	Product	Functional activity	Mechanisms of anti-TB drugs	Structure & Pubchem CID	References
katG (Rv1908c)	2,223	740	80,572.8	Catalase-peroxidase	Intracellular survival of mycobacteria	INH: Inhibition of mycolic acid synthesis Activity: Bactericidal	Pubchem CID: 3767	Ramaswamy et al., 2003; Vilchèze et al., 2006, 2007; Forrellad et al., 2013; Machado et al., 2013; Bantubani et al., 2014; Seifert et al., 2015; Zhang and Yew, 2015; Aye et al., 2016; Datta et al., 2016
InhA (Rv1484)	810	269	28,527.8	NADH-dependent enoyl ACP reductase	Mycolic acid biosynthesis
AhpC (Rv2428)	588	195	21,566.3	Alkyl hydroperoxide reductase	Protection against oxidative stress
FabG1 (Rv1483)	744	247	25,665.2	3-Oxoacyl (acyl-carrier protein) reductases	Fatty acid biosynthesis pathway
iniA (Rv0342)	1,923	640	70,082.9	INH inductible gene protein IniA	Efflux pump associated
FadE24 (Rv3139)	1,407	468	49,646.4	acyl-CoA dehydrogenase FadE24	Involved in lipid degradation and fatty acid β –oxidation
KasA (Rv2245)	1,251	416	43,284.1	β -Ketoacyl acyl carrier protein synthase	Involved in fatty acid biosynthesis
ndh (Rv1854c)	1,392	463	49,619	NADH dehydrogenase Ndh	Electrons transference from NADH to the respiratory chain
rpoB (Rv0667)	3,519	1172	129,218	β-subunit of RNA polymerase	Catalyzes the transcription of DNA into RNA	RIF: Inhibition of RNA synthesis Activity: Bactericidal	Pubchem CID: 5458213	Mboowa et al., 2014; Ocheretina et al., 2014; Thirumurugan et al., 2015; Aye et al., 2016
rpoA (Rv3457c)	1,044	347	37,706.5	α-subunit of RNA polymerase	Catalyzes the transcription of DNA into RNA
rpoC (Rv0668)	3,951	1316	146,737	β′-subunit of RNA polymerase	Catalyzes the transcription of DNA into RNA
pncA (Rv2043c)	561	186	19,604.6	Pyrazinamidase/nicotinamidase (PZase)	Converts amides into acid (PZA into POA)	PZA: Inhibition of trans-translation and pantothenate and CoA synthesis; depletes of membrane energy Activity: Bactericidal / bacteriostatic	Pubchem CID: 1046	Juréen et al., 2008; Shi et al., 2011b, 2014; Njire et al., 2016, 2017; Zhang et al., 2017
RpsA (Rv1630)	1,446	481	53,201.8	30S ribosomal protein S1	Translate mRNA with a shine-dalgarno (SD) purine-rich sequence
panD (Rv3601c)	420	139	14,885	Aspartate alpha-decarboxylase	Pantothenate biosynthesis
clpC1 (Rv3596c)	2,547	848	93,552.4	ATP-dependent protease ATP-binding subunit ClpC1	Protein degradation, Hydrolyses proteins in presence of ATP
gpsI (Rv2783c)	2,259	752	79,734.7	Bifunctional protein polyribonucleotide nucleotidyltransferase GpsI (pnpase)	Involved in mRNA degradation
rpsL (Rv0682)	375	124	13,849.2	30S ribosomal protein S12 RpsL	Translation initiation step	STR: Inhibition of protein synthesis Activity: Bactericidal	Pubchem CID: 19649	Finken et al., 1993; Sharma et al., 2007; Chakraborty et al., 2013; Du et al., 2013; Perdigão et al., 2014; Smittipat et al., 2016
rrs (MTB000019)	1,537	—	—	16S ribosomal RNA	Stable RNAs
gidB (Rv3919c)	675	224	24,031.9	7-methylguanosine methyltransferase	Probable glucose-inhibited division protein B Gid
EmbB (Rv3795)	3,297	1098	118,021	Arabinosyl transferase EmbB	Biosynthesis of the mycobacterial cell wa	EMB: Inhibition of arabinogalactan synthesis Activity: Bacteriostatic	Pubchem CID: 14052	Mikusová et al., 1995; Wang et al., 2010; Safi et al., 2013; Yoon et al., 2013; Moure et al., 2014; Zhang et al., 2014; Brossier et al., 2015; Xu et al., 2015
EmbA (Rv3794)	3,285	1094	115,692	Arabinosyl transferase EmbA	Biosynthesis of the mycobacterial cell wall
EmbC (Rv3793)	3,285	1094	117,490	Arabinosyl transferase EmbC	Biosynthesis of the mycobacterial cell wall
embR (Rv1267c)	1,167	388	41,933.5	Transcriptional regulatory protein EmbR	Regulator of embCAB operon transcription
rmlD (Rv3266c)	915	304	32,044.8	dTDP-4-dehydrorhamnose reductase	Involved in dTDP-L-rhamnose biosynthesis
gyrA (Rv0006)	2,517	838	92,274.3	DNA gyrase subunit A	Negatively supercoils closed circular double-stranded DNA	Fluoroquinolone: Inhibition of DNA synthesis Activity: Bactericidal	Moxifloxacin Pubchem CID: 152946	Aubry et al., 2004; Von Groll et al., 2009; Cui et al., 2011; Nosova et al., 2013; Li et al., 2014
gyrB (Rv0005)	2,142	675	74,058.7	DNA gyrase subunit B	Negatively supercoils closed circular double-stranded DNA
rrs (MTB000019)	1,537	—	—	16S ribosomal RNA	Stable RNAs	KAN/AMK/CAP/VIM: Inhibition of protein synthesis Activity: Bactericidal	Kanamycin Pubchem CID: 6032 Amikacin Pubchem CID: 37768 Capreomycin Pubchem CID: 3000502 Viomycin Pubchem CID: 3037981	Stanley et al., 2010; Ajbani et al., 2011; Yuan et al., 2012; Du et al., 2013; Reeves et al., 2013; Sowajassatakul et al., 2014; Freihofer et al., 2016
eis (Rv2416c)	1,209	402	43,771.8	Aminoglycoside N-acetyltransferase	Acetylation, intracellular survival
whiB7 (Rv3197A)	279	92	10,106.7	Transcriptional regulatory protein WhiB7	Transcriptional mechanism
TlyA (Rv1694)	807	268	28,042.1	2′-O-methyltransferase	Methylates 16S and 23S rRNA
InhA (Rv1484)	810	269	28,527.8	NADH-dependent enoyl ACP reductase	Mycolic acid biosynthesi	ETO: Disrupts cell wall biosynthesis Activity: Bacteriostatic	Pubchem CID: 2761171	Zhang et al., 1992; Vilchèze et al., 2006, 2008; Carette et al., 2011; Grant et al., 2016; Thee et al., 2016; Mori et al., 2017
ethA (Rv3854c)	1,470	489	55,326.1	Monooxygenase EthA	Activates the pro-drug ethionamide (ETH)
ethR (Rv3855)	651	216	23,724.7	Transcriptional repressor protein EthR	Regulates negatively the production of ETHA
KasA (Rv2245)	1,251	416	43,284.1	β -Ketoacyl acyl carrier protein synthase	Involved in fatty acid biosynthesis
thyA (Rv2764c)	792	263	29,820.8	Thymidylate synthase ThyA	Deoxyribonucleotide biosynthesis	PAS: Inhibits of folic acid and thymine nucleotide metabolism Activity: Bacteriostatic	PubchemCID: 4649	Rengarajan et al., 2004; Mathys et al., 2009; Zhao et al., 2014; Meumann et al., 2015
folC (Rv2447c)	1,464	487	50,779.3	Folylpolyglutamate synthase protein FolC	Conversion of folates to polyglutamate derivatives
dfrA (Rv2763c)	480	159	17,640	Dihydrofolate reductase DfrA	For de novo glycine and purine synthesis
RibD (Rv2671)	777	258	27,693.5	Bifunctional enzyme riboflavin biosynthesis protein RibD	Involved in riboflavin biosynthesis
alr (Rv3423c)	1,227	408	43,355.6	Alanine racemase Alr	Provides D-alanine required for cell wall biosynthesis	DCS: Inhibits the synthesis of peptidoglycan in the cell wall Activity: Bacteriostatic	PubchemCID: 6234	Cáceres et al., 1997; Andini and Nash, 2006; Chen et al., 2012; Zhang and Yew, 2015; Desjardins et al., 2016
ddl (Rv2981c)	1,122	373	39,678.2	D-alanine: D-alanine ligase DdlA	Involved in cell wall formation
Ald (Rv2780)	1,116	371	38,713.2	L-alanine dehydrogenase	Cell wall synthesis
cycA (Rv1704c)	1,671	556	60,047.2	D-serine / alanine / glycine transporter protein CycA	transport across the cytoplasmic membrane
Rv0678	498	165	18,346.7	Conserved protein	Transcription repressor for efflux pump MmpL5	CLO: Produces reactive oxygen, inhibits energy production, memberane distruption Activity: Bacteriostatic	Pubchem CID: 2794	Huitric et al., 2010; Yano et al., 2011; Hartkoorn et al., 2014; Almeida et al., 2016
Rv1979c	1,446	481	51,084.1	Conserved permease	Probably involved in transportation of amino acid across the membrane.
pepQ (Rv2535c)	1,119	372	38,758.9	Cytoplasmic peptidase PepQ	Possibly hydrolyses peptides
rplC (Rv0701)	654	217	23,090.5	Encodes the 50S ribosomal L3 protein	Formation of peptidyltransferase center of the ribosome	LIN/SZD: Both act by fixation of an early step in protein synthesis Activity: Bactericidal	Pubchem CID: 441401	Williams et al., 2009; Beckert et al., 2012; Makafe et al., 2016; Zhang et al., 2016
rrl (MTB000020)	3,138	—–	—–	Ribosomal RNA 23S	Stable RNAs
Ddn (Rv3547)	456	151	17,371	Deazaflavin-dependent nitroreductase	Converts bicyclic nitroimidazole drug candidate pa-824 to three metabolites,	DMD: Impeding the synthesis of mycolic acid Activity: Bactericidal	Pubchem CID: 6480466	Matsumoto et al., 2006; Palomino and Martin, 2014; Shimokawa et al., 2014; Bloemberg et al., 2015; Haver et al., 2015
Fgd1 (Rv0407)	1,011	336	490.783	F420-dependent glucose-6-phosphate dehydrogenase	Catalyzes oxidation of glucose-6-phosphate to 6-phosphogluconolactone using coenzyme F420 as the electron acceptor
fbiA (Rv3261)	996	331	3,640.54	F420 biosynthesis protein FbiA	Required for coenzyme F420 production: involved in the conversion of FO into F420
fbiB (Rv3262)	1,347	448	3,641.53	F420 biosynthesis protein FbiB	Required for coenzyme F420 production: involved in the conversion of FO into F420
fbiC (Rv1173)	2,571	856	1,302.93	F420 biosynthesis protein FbiC	Participates in a portion of the F420 biosynthetic pathway between pyrimidinedione and FO
mmpL3 (Rv0206c)	2,835	944	100,872	Conserved transmembrane transport protein MmpL3	Unknown; Supposed to be involved in fatty acid transport	SQ-109: Acts by interfering with the assembly of mycolic acids into the bacterial cell wall core Activity: Bactericidal	Pubchem CID: 5274428	Boshoff et al., 2004; Jia et al., 2005; Grzegorzewicz et al., 2012;
DprE1 (Rv3790)	1,386	461	50,163.2	Decaprenylphosphoryl-beta-D-ribose 2′-oxidase	Together with DPRE2 arabinan synthesis	BTZ: Drug is activated by reduction of an essential nitro group to a nitroso derivative, which can react with a cysteine residue in DprE1 Activity: Bactericidal	ChemSpider ID: 25941868	Manina et al., 2010; Trefzer et al., 2010; Kolly et al., 2014; Makarov et al., 2014
DprE2 (Rv3791)	765	254	27,468.8	Decaprenylphosphoryl-D-2-keto erythro pentose reductase	Together with DPRE1 arabinan synthesis