Measuring drug resistance is one of the challenging and essential pharmaceutical activities. It is a laborious and costly laboratory-based experimentation. Various clinical and experimental analyses for measuring drug resistance have been carried out. Results have been obtained for different types of therapeutic agents as a consequence of changes in the amino acids compositions in the sequence (mutation) of the organisms involved. In the same manner, the positions of these amino acids alterations and the level of resistance (folds) have also been experimentally identified. For example, G36S and V38M mutation in the Human Immunodeficiency Virus (HIV) Transmembrane glycoprotein (gp41) has been found to cause 100-fold resistance. However, there does not seem to have bioinformatics method developed in which the amino acid information of the proteins involved in the studies were used to computationally assess the degree of drug resistance without involving laboratory-based experimental procedure. The post-genomic era has witnessed the relevance of Bioinformatics approaches in the analysis of huge biomedical data. One such approach is the analysis of protein residues using digital signal processing technique such as informational spectrum method (ISM). Therefore, we propose a new bioinformatics method that is capable of assessing drug resistance without the use of any laboratory-based experiments. This new method incorporates ISM, sequence information of the proteins and other relevant information. By using the ISM and EIIP amino acid scale, the technique was applied in three classes of anti-HIV/AIDS drugs as a case study. It is observed that the protein residues of the susceptible strains attained the maximal peak amplitude at the consensus frequency while the resistant strains maintained lower amplitudes. This result signifies lower contribution from the resistant strains due to the mutation. The findings are consistent with those of the experimental ones and therefore suggest that the approach taken can be used to help assess drug resistance without laboratory-based experimentation. It should also be noted that the method can be applied in other drug resistance studies where sequence information of proteins is available and help design a computer-aided drug resistance calculator.

Resonant Recognition Model (RRM): Background Resonant Recognition Model (RRM) is a Digital Signal Processingbased technique, which recognizes protein primary structures or physiological functionalities as protein residues represented by numbers that are assigned from the Electron-ion Interaction Pseudopotenatial (EIIP) parameter [2]. RRM involves four steps, which are fully discussed below. The steps include: Step 1: Conversion of the Protein Residues into Numerical Values Electron-ion Interaction Pseudopotenatial (EIIP) Parameter: There are 20 essential amino acids constituents (protein residues) [7]. Biological interactions have been studied in relation to the behaviour of these 20 amino acids constituent of proteins. As a

Two HIV-1 non B isolates, 98US_MSC5007 and 98US_MSC5016, which have been identified amongst the US Army personnel serving abroad, are known to have originated from other nations. Notwithstanding, they are categorized as American strains. This is because their countries of origin are unknown. American isolates are basically B subtype. 98US_MSC5007 belongs to Circulating Recombinant Form (CRF02_AG) while 98US_MSC5016 is of the C clade. Both sub-groups are recognized to have originated from African and Asian continents. It has become necessary to properly determine the countries of origin of microbes and viruses. This is because diversity and cross-subtyping have been found to mitigate the designing and development of vaccine and therapeutic interventions. The aim of this study therefore is to identify the countries of origin of the two American isolates found amongst US Army personnel serving abroad. A Digital Signal Processing-based Bioinformatics technique called Informational Spectrum Method (ISM) has been engaged. ISM entails translating the amino acids sequences of the protein into numerical sequences (signals) by means of one biological parameter (Amino Acids Scale). The signals are then processed using Discrete Fourier Transform (DFT) in order to uncover and present the embedded biological information as Informational Spectra (IS). Spectral Position of Maximum Binding Interaction (SPMBI) is used. Several approaches including Phylogeny have preliminarily been employed in the determination of evolutionary trends of organisms and viruses. SPMBI has preliminarily been used to re-establish the semblance and common originality that exist between human and Chimpanzee, evolutionary roadmaps in the Influenza and HIV viruses. The results disclosed that 98US_MSC5007 shared same semblance and originality with a Nigeria isolate (92NG083) while 98US_MSC5016 with the Zairian isolates (ELI, MAL, and Z2/CDC-34). These results appear to demonstrate that the American soldiers harboring these strains may have been infected by isolates from Nigeria and Zaire, respectively. This is because 98US_MSC5007 and the Nigerian isolate share SPMBI at position 44. Additionally, 98US_MSC5016, which has SPMBI at position 148, may have come from Zaire as it has similar SPMBI with the Zairian isolates at 150. SPMBI is a demonstration of Bio-functionality arising from maximum affinity by the proteins from different sources to a common protein. To help validate the findings, the experiment was further repeated using ISM-based Phylogenetic technique. The outcome appears not to be in complete accord with the results obtained in this study. It is therefore recommended that the countries in which these US Army personnel are deployed be identified and where the findings made and the locations of the Army personnel appropriately correlate, this novel procedure be engaged in the identification of the nations of origins of all other such HIV isolates across all clades and nations.

The mechanism by which HIV infection transforms into AIDS disease is unclear. Several factors such as the decline in immune response, increase in replication rate, Syncytium inducing capacity and ability of the viruses to infect tumour cell lines are found to be associated with HIV progression to AIDS. What has not been investigated is the role of an increase in affinity for the CD4+ T cells by the HIV-1 T cell lymphocyte-loving (T-tropic) viruses. They are known to be mutants of the Macrophage-loving (M-tropic) viruses and dominate the late stage of the HIV infection in the disease progression. To elucidate the mechanism by which HIV is transformed into AIDS, this role is examined by using the Resonant Recognition Model (RRM). This is achieved by comparing the degree of affinity between the host CD4 and the gp120 from the HIV-1 M-tropic and HIV-1 T-tropic viruses as well as the isolates of HIV-2 and Simian immunodeficiency virus (SIV). The results reveal that only HIV-1 T-tropic viruses bind effectively to the CD4 suggesting that T-tropic viruses, which were identified to have mutated from the M-tropic viruses, acquire enhanced and long-lasting attachment to the CD4. This sustained affinity brings about continued attack on the diminishing CD4 until the immune system of the host collapses, which manifests clinically as AIDS. The findings therefore suggest an approach that should target the Variable region 3 (V3) of the HIV-1 gp120 at the early stage of the infection as a part of the HIV/AIDS management procedure. This procedure is essential as early initiation of HIV/AIDS therapy is generally assumed to prevent the spread of the virus and deterioration of the host immunity. The study is expected to help better understand the HIV pathogenesis and re-strategise pharmaceutical approaches to designing new HIV/AIDS therapeutic interventions.

The mechanism by which HIV infection transforms into AIDS disease is unclear. Several factors such as the decline in immune response, increase in replication rate, Syncytium inducing capacity and ability of the viruses to infect tumour cell lines are found to be associated with HIV progression to AIDS. What has not been investigated is the role of an increase in affinity for the CD4+ T cells by the HIV-1 T cell lymphocyte-loving (T-tropic) viruses. They are known to be mutants of the Macrophage-loving (M-tropic) viruses and dominate the late stage of the HIV infection in the disease progression. To elucidate the mechanism by which HIV is transformed into AIDS, this role is examined by using the Resonant Recognition Model (RRM). This is achieved by comparing the degree of affinity between the host CD4 and the gp120 from the HIV-1 M-tropic and HIV-1 T-tropic viruses as well as the isolates of HIV-2 and Simian immunodeficiency virus (SIV). The results reveal that only HIV-1 T-tropic viruses bind effectively to the CD4 suggesting that T-tropic viruses, which were identified to have mutated from the M-tropic viruses, acquire enhanced and long-lasting attachment to the CD4. This sustained affinity brings about continued attack on the diminishing CD4 until the immune system of the host collapses, which manifests clinically as AIDS. The findings therefore suggest an approach that should target the Variable region 3 (V3) of the HIV-1 gp120 at the early stage of the infection as a part of the HIV/AIDS management procedure. This procedure is essential as early initiation of HIV/AIDS therapy is generally assumed to prevent the spread of the virus and deterioration of the host immunity. The study is expected to help better understand the HIV pathogenesis and re-strategise pharmaceutical approaches to designing new HIV/AIDS therapeutic interventions.