Abstract: The invention provides a method of treating a microbial infection in a subject and a method of improving an immune system response in a subject against a disease, condition, infection, or virus thereof, by administering an effective amount of a nucleoside, short oligonucleotide compound or an analog thereof, or a pharmaceutically acceptable salt, racemate, enantiomer, diastereomer, geometric isomer, or tautomer thereof. In addition, the invention provides methods for treating or preventing a viral infection, bacterial infection, parasitic infection, or fungal infection in a subject (such as, a human). The compounds of the invention include, for example, di-, and trinucleotide compounds as provided herein. The compounds of the invention are useful for different therapeutic applications including, such as, prophylactics and therapeutics. The invention also provides design and synthesis of a compound that is useful for various therapeutic applications as mentioned herein.